FEDERAL MINISTRY OF HEALTH DEPARTMENT OF PUBLIC HEALTH

GUIDELINES
for

CLINICAL MANAGEMENT OF TB/HIV RELATED CONDITIONS IN NIGERIA

2nd Edition,

Table of contents
Table of contents ......................................................................................................................................... 2 Glossary of Abbreviations ........................................................................................................................ 3 Contributors: ................................................................................................................................................. 4 Foreword ........................................................................................................................................................ 5 Acknowledgements .................................................................................................................................... 6 Introduction ................................................................................................................................................... 7 Coordinating Care between TB and HIV Care Providers ............................................................. 7 Accessing TB/HIV Care/Services ....................................................................................................... 10 Diagnosis and Treatment of TB among PLHIV .............................................................................. 13 Prevention, Diagnosis and Care of HIV/AIDS among TB Patients ......................................... 25 TB/HIV Co-Infection in Children ........................................................................................................ 33 Prevention and Management of Opportunistic Infections. ...................................................... 43 Prevention of TB/HIV in Health Care Settings. ............................................................................. 46 ANNEX: ......................................................................................................................................................... 53

Glossary of Abbreviations
AFB AIDS ART Acid Fast Bacillus Acquired Immune Deficiency Syndrome Anti-Retroviral Therapy

DOTS DR-TB DST EIA EID

EPTB FCT FGN FMOH

Directly Observed Treatment Short Course Drug Resistant Tuberculosis Drug Susceptibility Test Enzyme Immuno Assay Early Infant Diagnosis

HAART

HCT HIV INH IPT MDR-TB NGO NTBLCP NTBLTC NASCP

NNRTI NRTI OI
PB PEP PHC

Extra-Pulmonary Tuberculosis Federal Capital Territory Federal Government of Nigeria Federal Ministry of Health Highly Active Anti retroviral Treatment HIV Counseling and Testing Human Immuno-deficiency Virus Isoniazid Isoniazid Preventative Therapy Multi-Drug Resistant Tuberculosis Non-governmental Organization National Tuberculosis and Leprosy Control Programme National Tuberculosis and Leprosy Training Centre National AIDS and STD control Programme

Non-Nucleoside Reverse Transcriptase Inhibitor Nucleoside Reverse Transcriptase Inhibitor Opportunistic Infections
Pulmonary Tuberculosis Post Exposure Prophylaxis Primary Health Care

PI

Protease Inhibitor Rifabutin Ribonucleic Acid

PLWHA PPM

People Living with HIV and AIDS Public-Private Mix for DOTS

Rfb RNA

TB WHO

XDR-TB

Tuberculosis World Health Organization

Extensively Drug - Resistant Tuberculosis

Contributors:
The Federal Ministry of Health would like to thank all those who actively participated in the adaption of the Guidelines for Clinical Management of TB/HIV related conditions in Nigeria. In particular, the Ministry wishes to acknowledge the inputs of the following individuals: J.O. Obasanya E. Nginge C. Adesingbin P. Akande E. Asadu A. O. Awe E. Asadu M. Babashani N. Chukwurah. N.C. Chukwueme S. Dutt J. Ganiyu M. Gidado A. Haruna T. Hussain Y. Habibu N. Ifebunandu M. Jose H.D. Liman Y. Mohammed C. Nwazue T.O. Odusote S. Ogiri S. Olanrewaju O. Oladapo E. Oyama C. Osakwe A. F. Omoniyi P. Patrobas M. Shaibu. E. Ubochioma

Foreword
TB and HIV constitute major public health problems in Nigeria. The burdens of these diseases are further compounded by the impact they have on each other, HIV fuels the burden of TB in the country while TB on the other hand is the commonest infection among People Living with HIV/AIDS (PLHIV). The interaction between these two diseases increases the morbidity and mortality among TB/HIV co-infected patients and also stretches the already challenged infrastructure of the health sector. Nigeria is among the 22 high TB burden countries that contributed 80% of the global TB burden (WHO report 2011: Global Tuberculosis Control). Similarly, the country has the second highest number of people living with the HIV/AIDS in the World after South Africa (UNAIDS HIV epidemic update 2010). The National HIV prevalence for 2010 is 4.1% (2010 National HIV Sero-prevalence Sentinel Survey (NHSS). The Federal Ministry of Health in its effort at providing effective and coordinated response to the dual epidemics of TB and HIV established the National TB/HIV Working Group in 2006. A Strategic Framework was developed as well as the National Guidelines for clinical management of TB/HIV related conditions in Nigeria. The Ministry has recorded significant progress since commencement of TB/HIV collaborative activities in the country; the proportion of registered TB patients accessing HIV Counseling and Testing (HCT) services in the country has increased from 10% in 2006 to 81.4% in 2011 with a current co-infection rate of 25%. The proportions of TB/HIV coinfected patients accessing CPT, ART and other HIV support services have also increased. Implementation of the 3Is (ICF, IPT and IC) have also recorded minimal progress though this is suboptimal and collective actions is required to scale up the implementation of 3Is and other TB/HIV collaborative activities in the country. The second edition of the Guidelines for Clinical Management of TB/HIV related conditions in Nigeria was therefore developed to support efforts at country level in scaling up implementation of TB/HIV collaborative activities taking into consideration lesson learnt on the field in the past 5 years and other global advancement. The guidelines will enhance the capacities of health workers involved in the caring of TB/HIV co-infected patient and are therefore an essential document for implementing partners providing support for TB/HIV collaborative activities at all level. Prof. C.O. Onyebuchi Chukwu Honorable Minister Federal Ministry of Health Abuja,

Acknowledgements
The Federal Ministry of Health wishes to express its gratitude to the numerous individuals and developmental partners who worked with the Ministry to review this document. Special thanks to all partners for their support and active participation in the whole process of developing this document. The FMOH appreciates the financial support received from WHO and USAID which made the production of this document possible

Mrs. Fatima Bamidele Permanent Secretary, Federal Ministry of Health August 2012

Introduction
Tuberculosis (TB) remains a serious public health problem in Nigeria with an estimated incidence rate of 133 per 100,000 and prevalence rate of 199 per 100,000 populations (WHO report 2011: Global Tuberculosis Control). 93,050 TB cases were notified in 2011 translating into a Case Detection Rate (CDR) of 43% for all forms of TB (2011 NTBLCP Statistics). Similarly, Nigeria has the second largest burden of HIV/AIDS in Africa with about 3.1 million estimated to be living with HIV in 2010 (Technical Report of 2010 National HIV sentinel Survey). The National HIV prevalence (after a drop between year 2001 and 2005) rose from 4.4% in 2005 to 4.6% in 2008 and dropped to 4.1% in 2010 (Technical Report of 2010 National HIV sentinel Survey) HIV is known to increase the burden of Tuberculosis while TB is the leading cause of death among People Living with HIV/AIDS (PLHIV) and is responsible for about 14-54% of HIV/AIDS deaths globally (WHO Stop TB Dept. estimates 2002). Therefore, it is imperative that health workers be on the alert for interactions between these two diseases and learn to manage conditions arising from them competently.

2. Coordinating Care between TB and HIV Care Providers

2.1. Introduction These Guidelines are targeted at general health care providers working at the facility level to provide directions in identifying common conditions associated with TB, HIV/AIDS and TB/HIV co-infection with a view to managing them appropriately. Medical officers who have been managing cases of TB or HIV/AIDS will also find these Guidelines useful especially as it pertains to the management of TB/HIV co-infection. The management of the TB/HIV patient co-infection should be patient-centered recognizing that there are two diseases, one patient and one health care system. As much as possible, care of TB and HIV patients should be seamlessly integrated to ensure this. If, however, there are separate TB and HIV care units at a facility, close collaboration and functional referral system should be ensured. In essence implementation of collaborative activities demand close collaboration at all levels of health care (See 2006 2010 National Strategic framework for implementing TB/HIV collaborative activities in Nigeria). 2.2 Membership and Terms of Reference of the TB/HIV Coordinating bodies (Working Groups) at all levels. 2. 2.1National, State and LGA levels

Membership of the Committee at National, State and LGA levels includes (not restricted to): Representative of the MOH HIV Program Managers (NASCP, SASCP, LASCP) TB Program Managers (NTBLCP, STBLCP, LGA TBLCP) HIV multisectoral response (NACA, SACA, LACA) Representative of all Implementing partners DOTS Providers especially at State and LGA levels. HIV Service Providers - especially at State and LGA levels. Ex- TB Patients Representative of TB Network/CSOs in TB Representative of PLHIV Network Representative of HIV/AIDS Civil societies Representative of Academia Media Religious leader Community member Terms of Reference of the working group at National/State/LGA levels are to support Government in: Promoting collaboration between TB and HIV/AIDS programmes as well as coordinating Implementing Partners (IPs) activities at various levels Developing/Adopting technical framework to guide all stakeholders for better TB control among HIV-infected people and effective HIV prevention and care among TB patients Reviewing and tracking progress of implementation of TB/HIV collaborative activities, identify challenges and proffers solutions Advocating for increased resources to control TB as a leading cause of illness and death among HIV-infected people as well as promoting socio mobilization activities on TB/HIV. Promoting Research in TB/HIV control and create data base on TB/HIV collaborative activities at all levels. Joint planning, implementation, monitoring and evaluation of TB/HIV collaborative activities. 2.2.2. At Facility level: The suggested membership of this committee includes: Hospital Management Staff from DOTS centers Staff from HIV centers Doctor i/c HIV services. Doctor i/c DOTS services. Laboratory Representative.

Pharmacy Representative. Representative of the support groups in the facility. LGA TBLS LGA HIV/AIDS programme managers.

Note: This coordinating committee can be in-cooperated into the existing committee in the facility where feasible The Terms of Reference of the TBHIV Committee at facility level includes: To review and track progress of implementation of TB/HIV collaborative activities in the facility. To establish/strengthen referral and linkages between TB & HIV services: the committee must ensure that referral and its outcomes in the facility between the TB and HIV units are properly documented. To identify challenges inhibiting effective service delivery and proffers solutions To plan, implement and monitor jointly TB/HIV activities To support facility staff in documentation of all TB/HIV services. All the TB/HIV information from both TB and HIV clinics should be crosschecked and updated during the meeting. A TB suspect register may be placed also at the HIV clinic to capture records of all TB suspects sent from the HIV clinic to the TB unit The TB/HIV working group or Committee may meet on monthly or quarterly basis. All secondary and tertiary institutions providing TB and HIV services should set up a TB/HIV committee at the facility level to enhance effective integration of TB/HIV services

3.

Accessing TB/HIV Care/Services

3.1 Definition of TB/HIV Care PLHIV and TB patients should have access to a variety of services/care aimed at improving their quality of life. The starting point should be the counseling of individuals for TB and HIV usually at Out-Patient Department (OPD) as well those suspects attending TB clinics. The available TB/HIV services include: Counseling for TB and TB/HIV interactions Counseling for HIV testing HIV Testing Diagnosis of TB Treatment of TB Preventing TB in PLHIV using Isoniazid Preventing common opportunistic infections using Cotrimoxazole in PLHIV Alleviating common conditions associated with HIV/AIDS e.g. oral thrush, sore throat, skin infections and diarrhea (palliative care) Anti-retroviral Therapy (ART) for HIV-positive clients Care and support services including community and home-based care Contact tracing and patient tracking Treatment adherence services Adherence counseling on Anti-TB care and ART Treatment Support Specialist (TSS)/Treatment partner.
3.2. Recommended procedures at TB and HIV Service points according to category of patients

3.2.1. Recommended procedure for every TB suspect (see Annex 1 Management of TB suspects) Take history and do physical examination Diagnose TB (in line with National algorithm) Start DOTS if TB is diagnosed Offered HCT to all TB suspects Refer for HCT if unavailable
Health workers must record this activity in the TB clinic suspect register

All TB suspects must be offered HCT

3.2.2. Recommended procedure for TB-positive patients with unknown HIV status Offer patient pre-test counseling Do HIV test Offer post-test counseling Follow procedures in b and c depending on results

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Continue DOTS Refer for HCT if unavailable

Health workers must record this activity on Patients TB treatment card and the clinic register

All TB patients should be offered HCT.

3.2.3. Recommended procedure for HIV-positive TB patients Ascertain that pre-test counseling has been done. Give post-test counseling Continue DOTS Give treatment for common conditions complained of by the patients. (e.g. pain, oral thrush and diarrhea ) Refer for Anti-Retroviral Treatment (ART) Refer if patients condition deteriorates All TB patients with HIV positive result should be offered CPT and ARV
Health workers must record this activity on Patients TB treatment card and the TB clinic register

3.2.4. Recommended procedure for HIV-negative TB patients Ascertain that pre-test counseling has been done Give post-test counseling Provide education on the need for TB treatment adherence Educate in HIV prevention, which should include abstinence, faithfulness and / or condom use Continue DOTS Advise patients to repeat HIV test after 3 to 6 months Repeat HIV testing for TB patients with HIV negative result after 3 months 3.2.5. Recommended procedure for all PLHIV during every visit to the HIV service delivery centers: Take history and do physical examination Screened for TB (ask PLHIV for history of current cough, Fever, weight loss and night sweats) Evaluate for TB if yes to any of the above questions Refer for IPT if no to all the above questions.
Health workers must record this activity on Care/ART treatment card and registers.

All PLHIV MUST be screened for TB at every visits

3.2.6. Recommended procedure for an HIV-positive patient with unknown TB status Confirm HIV result

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Take history and do physical examination Diagnose TB (refer to flow chart for TB Diagnosis) Manage as appropriate Refer for AFB microscopy if unavailable

3.2.7. Recommended procedure for HIV/AIDS patients referred to TB treatment centers Take history and do physical examination Do AFB microscopy Diagnose TB Start DOTS if TB is diagnosed Refer to medical officer if AFB microscopy is negative, such patients should be sent for testing using Gene Xpert MTB/RIF machine where available PLHIVs diagnosed with TB who are on ART should be referred to a medical officer. 3.2.8. Recommended procedures for children. (refer to chapter 2)

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4.

Diagnosis and Treatment of TB among PLHIV

Introduction TB is a bacterial disease caused by Mycobacterium tuberculosis. Tuberculosis infection occurs when a person carries the tubercle bacilli in the body but in small numbers and in a dormant state. Tuberculosis disease, however, occurs when the tubercle bacilli multiply and become numerous enough to overcome the bodys defenses and produce signs and symptoms. These signs and symptoms could be suggestive of pulmonary TB (PTB) where the lungs are the primary organ affected or Extra-pulmonary TB (EPTB) when other organs are affected. The commonest forms of Extra-pulmonary TB are: pleural effusion, lymphadenopathy, pericardial disease, miliary disease, meningitis, disseminated TB (with mycobacteraemia) 4.1 Diagnosis of TB among HIV Positive Adult Clients

PTB is still the commonest form of TB in HIV infected patients. The presentation depends on the degree of immunosuppresion. The table below shows how the clinical futures, sputum smear result and chest x ray appearance often differ in early and late HIV infection. Features of PTB Clinical features Sputum smear result Chest x-ray appearance Stage of HIV infection Early Late Often resembles post- Often resembles primary primary PTB PTB Often positive Often negative Often cavities Often infiltrates with no cavities

The mainstay for the diagnosis of TB among PLHIV under the Directly Observed Treatment Short Course (DOTS) strategy is still the sputum microscopy examination. The National Guideline recommends that three1 sputum samples be collected for diagnosis within 24 hours as shown in the table below: Table 4.1 Guide to Sputum Collection Days Day 1 Sample Sample 1 (Spot) Explanation Patient provides an on the spot sample under supervision. (Patient is then given the sputum container to take home for an early morning sample (sample 2) for the following day

This may be changed to two sputum for diagnosis in the future collected at early mornings

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Patients produces and brings early morning sample to Day 2 the clinic Sample 3 Patient produces another on the spot sample under (Spot) supervision Other investigations such as sputum culture, Gene-xpert (Xpert-MTB/RIF) and PCR are useful in diagnosing TB especially in HIV positive individuals who are smear negative depending on the available resources. Flow chart for the diagnosis of TB among PLHIV after collection of sputum samples.
Current cough, Cough 2 weeks and more among PLHIV collect 3 sputum specimens

Sample 2

Sputum AFB microscopy

AFB +, +, + AFB +, +, 0 AFB +, +, sc AFB +, sc, 0 AFB sc, sc, sc AFB sc, sc, 0

AFB +, 0, 0 AFB sc, 0, 0

AFB 0, 0, 0

Refer to Medical Officer for further investigation e.g. CXR, Gene-xpert

Yes TB

No TB

Manage as appropriate. Treat as TB

HIV positive clients with one sputum sample positive should be considered as a TB case 4.2 Classification of TB patients Case definitions

In order to prescribe appropriate TB treatment for HIV positive patients who developed TB, case definitions according to results of sputum microscopy and previous treatment are important. TB patients are classified as follows:

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New Case (N): A patient who has never had treatment for TB or who has taken antiTB drugs for less than four weeks. Relapse (R): A TB patient who was previously treated for TB, received Category 1(new case) treatment and was declared cured or completed a full course of treatment and has once again developed sputum smear-positive TB. Treatment failure (F): A patient who while on Category 1 treatment, remained or became smear-positive again five months or later after commencement of treatment. Return after default (RAD): A TB patient who completed at least one month of treatment (category 1) and returned smear-positive after at least 8 weeks of interruption of treatment. Transfer in (T. I.): A TB patient already registered for treatment in one LGA who is transferred to another LGA where (s)he continues treatment. Other (O): A TB patient who does not easily fit into any of the above case definitions e.g a. A patient who has been treated for TB outside the NTBLCP network for more than 4 weeks. b. A patient who previously receive treatment and was declared cure or completed a full course of treatment and is again diagnosed by medical officer as sputum smear negative TB c. A patient who previous received treatment but outcome of treatment is unknown and now smear positive

4.3. Treatment of TB among HIV Positive Adult Clients 4.3.1 Diagnostic Categories Based on case definition, all TB patients (adults and children) fall into a diagnostic category for treatment, as shown in the table below. Table 4.2 Anti-TB Treatment Categories Category Category 1 Category 2 Duration in months/ Drug Indication Combination 2RHZE/4RH Short-course chemotherapy for new cases 2SRHZE, 1RHZE/5RHE Re-treatment chemotherapy for relapses, failures, RAD and others

4.3.2 Treatment Regimens A treatment regimen consists of two phases

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1. The initial intensive phase of fully supervised daily administration of drugs is 2 months for new cases (Cat. 1) and 3 months for re-treatment cases (Cat. 2). 2. The continuation phase of treatment for new cases (Cat. 1) is 4 months of RH monthly drug collection by the patient. Patients on RH should be observed daily. For re-treatment cases (CAT II), the continuation phase is 5 months of RHE and should be supervised daily or thrice weekly. 4.3.3 Drugs and dosages for TB treatment in HIV clients: The drugs used in the treatment of TB in HIV clients are: R Rifampicin; E Ethambutol H Isoniazid; S Streptomycin Z Pyrazinamide ;

The dosages for the different categories and regimens are shown in the following tables Treatment Regimens: Fixed Dose Combinations (FDC) ADULTS
Category 1 Regimen for New Cases): 2RHZE/ 4RH

Regimen > 70 kg Intensive phase: daily supervised for 2 months Combined tablet of RHZE (150mg + 75mg + 400mg + 275mg)
Continuation phase: daily supervised for 4 months Combined tablet of RH (150mg + 75mg)

Pre-treatment weight 55-70 kg 38-54 kg 4

4

30-37 kg 2
2

5
5

3
3

Remark: If the patient weighs less than 30 kg, he should be given loose tablets.
Category 2 Regimen for Relapses, Failures, RAD and Others: 2SRHZE/RHZE/5RHE

Regimen Intensive phase: daily supervised for 3 months Combined tablet of RHZE (150mg + 75mg + 400mg + 275mg)
Add in the first two months daily:

> 70 kg 5 1 gram
5

Pre-treatment weight 55-70 38-54 30-37 kg kg kg 4 1 gram

4

3 0.75 gram
3

2 0.5 gram 2

Streptomycin

Continuation phase: daily intake for 5 months, supervised

Combined tablet of RHE (150mg + 75mg + 275mg)

i. Streptomycin should NOT be given to pregnant women.

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ii. Patients >45 years should not be given more than 0.75g of streptomycin irrespective of weight
4.3.4. Recommendations for individuals with TB Disease and HIV Co-Infection: a. In patients on rifampicin based anti-TB combinations avoid the use of Nevirapine and most Protease Inhibitors (PI). Nevirapine- containing regimen should be substituted with Efavirenz ( EFV) containing regimen. b. Patients on ART who develop TB should have the ARVs reviewed to accommodate the use of Rifampicin in the anti-TB regimen. c. In patients on a PI- based initial or subsequent ART regimen, rifabutin should be substituted for rifampicin. d. In patients whose initial indication for a PI based 1st line regimen was temporary, consider switching to Efavirenz when such patients develop TB and require rifampin based therapy.

Health workers at DOTS clinic must ask every HIV positive patients for history of ARVs before initiating TB treatment, the ARV regimen must be recorded on the patient TB treatment card and the clinic register

Rifampicin should not be used with Nevirapine and most PIs when treating TB and HIV.

Refer to the table below for different case scenarios involved in the management of TB/HIV co-infected patient Scenario Action Newly registered TB patients Start Cat I TB treatment immediately. diagnosed with HIV commence ART within 2 weeks of anti TB and not later than 8 weeks (irrespective of the CD4 count) Initiate CPT TB patients on continuation Continue TB treatment. phase of treatment diagnosed Start ART (Substitute Nevirapin with Effavirenz) with HIV Initiate CPT. PLHIV on ART who developed Continue ART (Substitute Nevirapin with TB Effavirenz) Start TB treatment immediately Continue/initiate CPT Reassess for ART Failure PLHIV on second line ART who Reassess for ART failure developed active TB Continue ART Start TB treatment immediately, change anti TB to loose drugs with Rifabutin containing regimen. Pregnant PLHIV on ART who Continue ART (Give 1st line avoiding Effavirenz in developed TB the 1st trimester) Start TB treatment immediately (Streptomycin is contraindicated in pregnancy) Continue/Initiate CPT (avoid CPT in 1st trimester)

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 Pregnant woman on TB treatment tested positive for HIV A child with TB who tested HIV positive

Reassess for ART failure Continue TB treatment Refer for PMTCT or ART clinic to determine eligibility and choice of ARV regimen Continue TB treatment. Refer to Pediatrician

All TB/HIV co-infected patients should commence ART within 2 weeks of anti TB and not later than 8 weeks (irrespective of the CD4 count)

4.3.5 Monitoring TB treatment among HIV clients. Monitoring progress of tuberculosis patients while on treatment is an essential part of case management. This is to ascertain the effectiveness of the drugs in killing M. tuberculosis as well as assessing improvement in the patients clinical state. Monitoring is done through the following methods: Sputum microscopy: Examine sputum for AFB at specified intervals Clinical: Conduct clinical assessment including weight assessment Drug intake: Assess patients records for regularity.

Two sputum smear examinations (taken as two early morning samples within 2 days) are done at different points during treatment: Cat 1: 6 months regimen; smear positive patients should be examined at end of 2nd months, 5th months and 6 months. CAT 2: 8 months regimen, smear positive patients should be examine at the end of 2 months, 5th months and 7 months

All sputum samples are to be collected one week prior to the end of month specified above If patient no longer produces sputum, but saliva instead, the laboratory should examine these materials for AFB For smear-negative patients only at the end of the 2nd month.

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4.4

Monitoring TB treatment among HIV clients.

Monitoring progress of tuberculosis patients while on treatment is an essential part of case management. This is to ascertain the effectiveness of the drugs in killing M. tuberculosis as well as assessing improvement in the patients clinical state. Monitoring is done through the following methods: Sputum microscopy: Examine sputum for AFB at specified intervals Clinical: Conduct clinical assessment including weight assessment Drug intake: Assess patients records for regularity.

Two sputum smear examinations (taken as two early morning samples within 2 days) are done at different points during treatment: Cat 1: 6 months regimen, smear positive patients should be examined at end of 2nd months, 5th months and 6 months. CAT 2: 8 months regimen, smear positive patients should be examine at the end of 2 months, 5th months and 7 months

All sputum samples are to be collected one week prior to the end of month specified above If patient no longer produces sputum, but saliva instead, the laboratory should examine these materials for AFB For smear-negative patients only at the end of the 2nd month.

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Table 4.6: Guide to monitoring TB treatment among HIV Positive on CAT 1 Regimen When?
End of 2 months

What do I do? Result?

2 sputum specimen Positive

Conclusion?
Intensive Rx not enough Intensive Rx enough Treatment failed Patient improving Treatment failed Excellent!

Action!
Extend 1 month, send sample for rapid DST Start Continuation

Negative

End of 5 months

2 sputum specimen

Positive

Start CAT II Rx, send sample for rapid DST

Negative

Continue Rx Start CAT II Rx, send sample for rapid DST Give last Rx DECLARE CURED!

End of 6/7 months

2 sputum specimen

Positive Negative

Table 4.7: Guide to monitoring TB treatment among HIV Positive on CAT 2 Regimen When? What do I do? Result? Conclusion? Action!

End of 3 months

2 sputum specimen

Positive

Intensive Rx not enough Intensive Rx enough Treatment failed Patient improving Treatment failed Excellent!

Extend 1 month!, Send sample for rapid DST Start Continuation

Negative

End of 5 months

2 sputum specimen

Positive

Continue Rx, Send sample for rapid DST

Negative

Continue Rx Continue Rx , Send sample for rapid DST Give last Rx DECLARE CURED!

End of 7 months

2 sputum specimen

Positive

Negative

Note: All Cat 1 and 2 failures should be referred for rapid DST

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4.5

Side-effects of anti-TB drugs:

Adequate treatment of each case for the full duration of the prescribed regimen is very important if success in treatment is to be achieved. Anti-TB drugs, however, are toxic and side-effects may occur. Some of these side-effects require treatment to be stopped immediately while some others require only treatment modification as shown in the tables below: Table 4.7 Adverse drug reactions that require treatment to be stopped SIDE-EFFECT POSSIBLE CAUSE ACTION

General reaction including Rifampicin shock, purpura and fever Pyrazinamide Streptomycin Impairment of vision in a Ethambutol patient on Ethambutol Jaundice (Yellowness of the Isoniazid eye) Rifampicin Pyrazinamide

STOP treatment and refer to the medical officer.

Note: 1. Patients who are pregnant must not be given streptomycin due to the risk of damage to the ear of the fetus Table 4.8 Adverse drug reactions that do not require treatment interruption SIDE-EFFECT POSSIBLE ACTION CAUSE Giddiness (staggering / Streptomycin Reduce dosage by one quarter, but if it loss of balance) persists for more than one week stop and refer to the Medical Officer. Severe nausea & vomiting Rifampicin Give the Rifampicin after food Skin rash in a patient not Isoniazid If patient is clinically well (not advanced on Thiacetazone Streptomycin TB or serious forms such as meningitis or Pyrazinamid disseminated disease) stop and resume e when the reaction has subsided. If symptoms recur, refer to Medical Officer Numbness or tingling Isoniazid Supplement with tab. Vit. B6 at a dose of sensation on the 100mg daily extremities Joint pains Pyrazinamid Check the dosage by weight as it is e usually caused by over-dosage.

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Red/orange urine

coloured Rifampicin

Easily alleviated with Aspirin (600 mg tds x 5 days). Pcm 25mg/Kg recommended for children Reassure patient

Note: 1. Any change to the treatment regimen due to side effects must be made only after careful consideration. 2. Challenging and desensitization should be done in referral hospitals only. See NTBLCP Guide for Medical Officers. 4.5.1. Reporting adverse drug reactions Reporting of suspected adverse reaction is important for promoting drug safety and rational drug use. All observe/suspected cases to anti tuberculosis and ARV drugs should be documented and reported using NAFDAC adverse drug reaction form.(Refer to annex) Steps for reporting ADR to anti TB/ARV drugs by Health Care Workers TB/HIV clients suspected of developing adverse drug reaction should be referred to medical officer Medical officer to take history (including detailed drug history, time relationship) physical examination and ancillary investigation to confirm diagnosis of adverse drug reaction Medical officer to check the known pharmacology of the medicine Fill the ADR Form for each TB/HIV co-infected clients confirmed to have features of adverse drug reaction) Form to be submitted to NAFDAC desk officers in each LGA 4.6. Treatment interruption TB/HIV co-infected treatment are likely to interrupt treatment because of the pill burden and overlapping toxicity from the two classes of drugs if patients are not properly counseled (adherence counseling) and supported while on treatment. This should be prevented as much as possible because of the risk of developing resistant among those who interrupted treatment, when it occurs, the procedure for managing treatment interruption are described below. New cases: Any individual who has not come to receive his/her treatment for two consecutive days during the intensive phase, or has failed to collect drugs for two weeks after the expected date during the continuation phase should be regarded as having interrupted treatment and therefore be traced. Defaulter tracing visit should be carried out and the corresponding report attached to the treatment card. Re-treatment Regimen: Any individual who has not come to receive his/her treatment for two consecutive days should be regarded as having interrupted treatment and therefore

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be traced. Defaulter tracing visit be carried out and the corresponding report attached to the treatment card .(SOP for defaulter tracking) Table 4.9 Interruption of anti-TB treatment among PLHIV Action required: 1st Action Trace patient Solve the cause of interruption Continue treatment and prolong it to compensate for missed doses Length of interruption < 1 month Do a smear? No Result of smear Duration of treatment Treatment Continue Rx and prolong to compensate for missed doses Continue Rx and prolong to compensate for missed doses Continue Rx and prolong to compensate for missed doses, send sample for rapid DST Cat 1: Start Cat 2 and send sample for rapid DST Cat 2: Send sample for rapid DST and continue treatment Clinical decision on individual basis whether to restart or continue treatment, or no further treatment Cat 1: Start Cat 2 and send sample for rapid DST Cat 2: Send sample for rapid DST and continue treatment

1-2 months

Yes (3 samples)

Negative or EPTB If 1 or more positive

< 5 months

> 5 months

2 or more months

Yes (3 samples)

Negative or EPTB

If 1 or more positive

PLHIV who interrupted treatment are likely to develop drug resistant TB, All PLHIV who interrupted treatment MUST therefore be immediately traced.

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4.7 Treatment of DR-TB/HIV The treatment of DR-TB in HIV Positive patients is similar to that in patients without HIV but the following should be noted: ART plays a crucial role, as mortality in MDR-TB/HIV patients without the use of ART is extremely high (91100%). Adverse effects are more common in patients with HIV infection. Overlapping toxicities exist with both 2nd line anti-TB treatment and ART. The multiple drugs involved in the management of DR-TB and HIV infection increases the pill burden, increasing the risk of sub-optimal adherence to medications. Ototoxicity (impaired hearing) may occur. All PLHIV with DR-TB should be managed at the designated treatment centers in the country.

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5.

Prevention, Diagnosis and Care of HIV/AIDS among TB Patients

5.1 Introduction Acquired Immune Deficiency Syndrome (AIDS) is caused by a virus known as the Human Immunodeficiency Virus (HIV). Since the first description of AIDS in 1981, infection has been on the increase. By 2010, there were an estimated 3.1million adults and children living with HIV or AIDS in Nigeria. Of these 2.81 million were adults and 321,580 children (Technical Report of 2010 National HIV sentinel Survey) HIV damages the human immune system, thereby impairing the capacity of the body to fight infectious organisms. As HIV infection progresses and immunity declines, patients become more susceptible to infections. These include TB, pneumonia, recurrent fungal infections and herpes zoster these are known as opportunistic infections (OIs) and they account for most of the ill health associated with HIV/AIDS. There is ample evidence that active management of OIs in persons living with HIV/AIDS as an adjunct to HAART greatly reduces the mortality and morbidity associated with HIV infection. 5.2 Diagnosis of HIV among TB patients

5.2.1. Laboratory diagnosis of HIV infection is based on the demonstration of antibody in plasma or serum, and of virus in the blood. A person who has recently been infected may not yet be making antibodies to the virus. The HIV test detects the antibodies to the virus, not the virus itself. In this case, the test would not detect antibodies against HIV in the blood. This time is often called the window period There are 2 categories of tests for diagnosis of HIV infection 5.2.2 Antibody Tests The most widely available way of identifying HIV-infected individuals is the detection of HIV antibodies in serum or plasma samples. HIV diagnostic tests are extremely reliable, and are highly sensitive and specific. The reliability of the tests depends on proper collection and testing on the part of the laboratory test. The table below shows the main methods of testing for HIV antibodies. 5.2.3. Antigen detection method This is the detection of the virus/viral particles in a patients blood sample DNA PCR useful and reliable test RNA PCR (viral load) this is the most sensitive test

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5.3.

Screening procedure for HIV testing

Serial algorithm is the nationally adopted screening procedure for HIV testing. This refers to the use of 2 screening tests sequentially to test for HIV antibody. The initial screening is done with a very sensitive test (in this case- determine). If the result of the first test is positive, the sample is subjected to a second test which is very specific (e.g. Unigold). A discordant result at the end of the second test require additional test which is referred to as tie breaker: e.g Stat pack. A positive tie breaker result means that the client is infected with HIV. Figure 4.1 National Serial testing algorithms Serial Testing

Blood Sample

Test 1

Negative Give Result

Positive Result

Positive Result Give Result

Discordant Result
Retest after 6 weeks, if still discordant refer to reference lab

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5.3

Anti-Retroviral Therapy (Art) For TB/HIV Co-Infected Patients

5.3.1 Classes of ARVs There are 6 classes currently available for treatment based on the site and mechanism of action. Other classes are at various stages of development but are not yet widely available for clinical use. i. Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) such as nevirapine and efavirenz stop HIV production by binding directly onto the reverse transcriptase enzyme thus preventing the transcription of viral RNA to DNA. A recent addition to this class is etravirine. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs/NtRTIs) incorporate themselves into the DNA of the virus, thereby stopping the building process. The resulting DNA is incomplete and cannot create a new virus Protease Inhibitors (PIs) work later in the virus reproduction cycle. They prevent HIV from being successfully assembled and released from the infected CD4+ cell. The chemokine receptors antagonists which bind to CCR5 or CXCR4 on the T cell surface and thereby prevent viral attachment to these co-receptors. This class includes Maraviroc Fusion inhibitors which bind to viral gp41 and prevent the virus from penetrating the T-cell membrane such as enfuvirtide Integrase Inhibitors: prevent the integration of viral DNA into the T-cell DNA and as such permanent infection of the cell is aborted and reproduction of viral RNA genome cannot occur neither can transcription of viral mRNA occur. An integrase inhibitor now available for clinical use is raltegravir.

ii. iii. iv. v. vi.

The following drugs and Fixed Drug Combinations have been licensed for use in Nigeria. Table 5.3.1: ARTs currently registered with NAFDAC Nucleoside/ [Nucleotide] Reverse Transcriptase Inhibitors (NsRTIs) Zidovudine (AZT, ZDV) Didanosine (ddl) Lamivudine (3TC) Abacavir (ABC) [Tenofovir(TDF)] Stavudine (d4T) Non-Nucleoside Reverse Protease Transcriptase Inhibitors (PIs) Inhibitors (NNRTIs) Nevirapine (NVP) Efavirenz (EFV) Saquinavir (SQV) Ritonavir (RTV) Indinavir (IDV) Nelfinavir (NFV) Amprenavir (APV) Lopinavir/Ritonavi r Atazanavir(ATZ) Fixed dose combinations*

TDF+FTC /3TCZ DV+3TC+NVP ZDV+3TC ABC+ZDV+3TC` LPV/r TDF+3TC+EFV

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* Fixed dose combinations (FDC) are based on the principle of inclusion of two or more active pharmacological products in the same tablet, capsule or solution. Stavudine is phased out and should only be used in patients with renal impairment when TDF and ZDV are contraindicated ATZ will soon be available and will be the preferred PI IDV will soon be phased out The first line drugs being used in Nigeria are Zidovudine, Tenofovir , Lamivudine, Stavudine , Efavirenz and Nevirapine . 5.4 ART Regimens and Doses in TBHIV co-infected patients The preferred ART regimen for TB/HIV co-infected patients are: For Rifampicin-containing regimen [(ZDV or TDF )] +[3TC or FTC] + EFV For non Rifampicin-containing continuation phase regimen [(ZDV or TDF ] +[3TC or FTC] + [EFV or NVP] For pregnant women (ZDV+3TC+EFV if beyond 1st Trimester) or (ZDV + 3TC + ABC) For patients who are poorly tolerant of EFV, (ZDV + 3TC +NVP) OR (TDF +3TC or FTC+NVP) OR ( ZDV+ 3TC+ABC or TDF) For those with hepatitis (B or Alcoholic) , ZDV+3TC+TDF The table below shows the first line ART regimens and doses. In managing patients who are dually infected with TB, Efavirenz is substituted for Nevirapine because Rifampicin, a first line drug in the management of TB, lowers the serum concentration of Nevirapine & vice versa. Table 5.1: ARVs and Dosages Drug Strength/Prepa ration for adults Lamivudine 100mg, 150mg (3TC) tablets Emtrcitabin 200mg e (FTC) Adult dosing Comments

150 mg BD or May be taken taken 300mg OD 300mg OD as prescribed by physician 200mg OD Closely related to 3TC and should not be co-administered with it

Zidovudine (ZDV)

100mg capsule, 250 300 mg Use with caution in the setting of 300mg tablets BD anaemia. Increased toxicity possible when used with other drugs that are associated with bone marrow suppression. Should not be administered in

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Abacavir (ABC) Tenofovir TDF Efavirenz (EFV) Nevirapine (NVP)

combination with d4T. Store at 15-25oC 300 mg tabs 300 mg BD or Causes hypersensitivity reaction 600mg OD (HSR), which can be fatal; never re-challenge the patient. Educate patient on HSR 300 mg tab 300mg OD Caution should be taken in renal impairment and renal function in particular. Plasma creatinine should be monitored. 200mg, 600mg 600mg OD * Contraindicated below 3 years of capsule age and in early pregnancy 200mg tablet 200mg BD, always initiate 200mg OD for 2 weeks before giving full dose. Increase incidence of severe hepatotoxity in women with CD4 count > 250/ml and men with CD4 count > 400 /ml. Other common reactions include skin rash. Should not be used with Rifampicin.

Dose adjustments may be necessary with renal impairment. *(information on benefits of 800mg EFV still awaited for patients >60kg 5.5 When to start Antiretroviral Therapy in PLHIV with TB For patients with active TB in whom HIV infection is diagnosed and ART is required the first priority is to initiate standard anti-TB treatment (in accordance with National TB policy and Guidelines). It is now recommended to start ART as soon as possible, preferably within 2 weeks but not later than 8weeks after starting Anti-TB drugs. 5.5.1 An EFV-containing regimen is the preferred first-line regimen. An alternative include NVP-containing regimen or triple NRTI (ZDV+3TC+ABC or TDF) . For NVPcontaining regimens, ALT should be checked at 4, 8 and 12 weeks; treatment should be decided on the basis of symptoms thereafter. 5.5.2 ART should start as soon as TB treatment is tolerated, particularly in patients with severe immunosuppression. 5.5.3 ART should be started if other non-TB stage 3 or 4 events are present after putting on treatment for the OIs.

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Note: 1. Refer TB patient with HIV positive result to ART sites for commencement of ART 2. Refer children to pediatricians for commencement of ART 5.6 Tuberculosis in patients already receiving ART There are two issues to consider in patients who are diagnosed with TB while on ART. The first concerns the modifications of ART, if any, which should be recommended for patients developing active TB within six months of initiating first-line or second-line ART. These recommendations are summarized in Table 7.4.

Table 5.6 ART recommendations for patients who develop TB within six months of starting a first-line or second-line ART regimen FIRST-LINE OR SECOND- ART REGIMEN AT THE OPTIONS LINE ART TIME TB OCCURS Two NRTIs + EFV Continue with two NRTIs + EFV Two NRTIs + NVP Substitute to EFVab or Substitute to triple First-line ART NRTI regimena or Continue with two NRTIs + NVPa Triple NRTI regimen Continue triple NRTI regimen Second-line ART Two NRTIs + PI Use Rifabutin in place of Rifampicin a Substituting back to the original regimens once the rifampicin-containing regimen is completed can be considered. When switching back from EFV to NVP, no lead-in dose is required. b The use of EFV-containing regimens is not recommended in women of childbearing potential, if adequate contraception cannot be ensured, and during the first trimester of pregnancy. c Careful clinical and laboratory monitoring (ALT) is advised when NVP is administered concurrently with rifampicin

The second issue is whether the presentation of active TB on ART constitutes ART failure. An episode of TB can occur across a wide range of CD4 cell counts and does not necessarily herald ART failure and the need to switch to second-line regimens. In

30

addition, sub clinical or undiagnosed TB often presents within the first six months after the initiation of ART, frequently as part of IRIS. Recommendations: If an episode of TB occurs during the first six months following the initiation of ART, this should not be considered a treatment failure event and the ART regimen should be adjusted for co-administration with Rifampicin-containing regimens If an episode of TB develops more than six months after the initiation of ART and data on the CD4 cell count and viral load are available, the decision about whether the TB diagnosis represents ART failure is based on the CD4 cell count and, if available, the viral load. If a CD4 cell count is not available the decision on whether the TB diagnosis constitutes ART failure depends on whether the TB is pulmonary or extra pulmonary and whether there are other non-TB stage 3 or 4 events. WHO recommends that the development of an episode of pulmonary TB after six months of ART, without other clinical and immunological evidence of disease progression, should not be regarded as representing ART failure. Extra pulmonary TB should be considered as indicating ART failure, although simple lymph node TB or uncomplicated pleural disease may be less significant than disseminated TB. o If there is a good response to TB therapy, the decision to switch to a secondline regimen can be delayed until short-course TB therapy has been completed. 5.6 Side-effects of Antiretroviral Therapy Monitoring of patients receiving ART is of utmost importance due to the interactions and adverse drug reactions produced by some of the drugs. Table 4.6 shows some common complaints to be expected from patients on ART, the possible offending drug and the recommended action to be taken. Table 5.6: Drug interactions / side-effects and recommended actions Symptoms/ signs Possible offending drug Headache, anaemia, sepsis, low Zidovudine white blood cell count Facial/ body swelling , reduced Tenofovir(TDF) urine out put Headache, fatigue, abdominal Lamivudine upset, numbness of hands and feet Abnormal liver function tests, Nevirapine severe hypersensitivity reactions, rash Action to be taken Refer for specialist care: Monitoring FBC Renal function test(creatitine clearance) adjust dosage Monitor, withdraw drug if symptoms are severe If LFT is suggestive of hepatitis or if jaundice is present discontinue; if rash is 31

severe discontinue. NoteRifampicin, Isoniazid, Pyrazinamide can cause abnormal liver function tests. There may be need to replace Nevirapine with Efavirenz. Rash may appear CNS side effects that include: H-hallucinations I-insomnia A-abnormal dreams S-somnolence A-amnesia A-abnormal thinking C-confusion E-euphoria For these reasons, EFV is contraindicated in patients who already have psychiatric manifestations, nightmares, rash. Efavirenz CNS symptoms often

resolve within 2-4 weeks. Potentially hence teratogenic should efavirenz

not be used in pregnant women in 1st trimester or women therapy. Monitor and withdraw drug if symptoms are severe who might become pregnant while on

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5.
6.1

TB/HIV Co-Infection in Children

Introduction:

Tuberculosis (TB) is a common opportunistic infection in HIV-infected children. Children get infected with TB when they come in contact with an infectious adult. HIV-positive children are at risk of diagnostic error as well as delayed diagnosis of TB because of overlapping clinical and radiographic features with other lung diseases. The gold standard of TB diagnosis, sputum smear microscopy, is often not feasible because children rarely produce sputum, and also smear microscopy is seldom helpful because yield is very low. This is even more so in the HIV-infected child. Mantoux test is less reliable especially in the HIV-infected child. TB manifestations are more severe in HIV-positive children and progression to death is more rapid than in HIV-negative children. The response to standard short-course therapy in HIV-positive children may not be as good as in HIVnegative children due to lower cure rates and higher mortality if not given in conjunction with ARVs for children that are eligible. 6.2 Diagnosis of TB in HIV Infected Children

It is difficult to diagnose PTB in children and even more so in HIV-infected ones because: several HIV-related diseases including TB present in the same way weight loss is a common problem in HIV-positive children; and Interpretation of the tuberculin skin test (Mantoux Test) is even more unreliable than usual. An immunocompromised child may have a negative Mantoux Test despite having TB

Children suspected of having TB by GHCWs should be referred to medical officer who will make the diagnosis based on: History and physical examination Sputum smear examination Mantoux test Chest x-ray lung biopsy (where available) Gene Xpert TB diagnosis in children is challenging; WHO Score Chart will assist MO in making this diagnosis.

Score Chart for the Diagnosis of Tuberculosis in Children

SCORE IF SIGN OR SYMPTOM IS PRESENT 0 1 2 3 4 Score

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GENERAL FEATURES Duration of Less than 2-4 weeks More than illness 2 weeks 4 weeks Failure to Weight No weight thrive or gain gain weight loss Proven TB contact None Reported Smear+ /EP not proven Tuberculin test Malnutrition Positive Not improved after 4 weeks No response to antibiotics TB suggestive feature like infiltration, cavity or hilar lymph nodes Cervical, submandibular Suggestive feature on X-ray Without With abdominal abdominal mass mass Chronic C.N.S. signs

Weight loss Proven Smear+

Chronic infant disease LOCAL FEATURES Chest x-ray

Recurrent

Lymph nodes Swelling of bone or joint Ascitis Meningitis Angle deformity of the spine TOTAL SCORE

X-ray feature

A score of 7 or more indicates a high likelihood of tuberculosis

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Interpretation of the result using the score chart

Flow Chart for Diagnosis of TB in Children

If Score < 7

If Score > 7

No X-Ray available

Chest X-Ray

Not diagnostic

Diagnostic for TB: Wide mediastinum, miliary shadows, cavities

Start TB Treatment

High dose antibiotics x 7/7

Poor response

Different antibiotic x 7/7

Poor response

Good response

No TB

Good response

Note that HIV-infected children may present with Extra-pulmonary TB or may be smear negative. EPTB often co-exist with PTB in children. All children with EPTB should be screened for PTB 6.3. Diagnosis of HIV in children with TB
HIV infection in children may show in many ways. The clinical signs are often non-specific and the diagnosis of HIV in young children is often very difficult. All children with TB should be screened for HIV infection. Parents (preferably both but at least the mother) of children suspected of TB disease should have HCT All children with TB should have HCT

35

6.3.1. HIV testing in children with TB: The diagnosis of HIV in children with TB is the same as that for children without TB A child is HIV infected if the following criteria are met: 1. The child is less than 18 months; With positive HIV DNA PCR using Early Infant Diagnosis (EID); or is born to an HIV positive mother with: o Positive antibody test and/or o meets the clinical criteria for AIDS diagnosis based on the WHO staging system (see Guidelines for Antiretroviral Therapy in Nigeria) 2. A child is 18 months or more with positive HIV antibody detection; or meets any criteria outlined in (1) above. Clinically, in children under 18 months old, the diagnosis of HIV infection is based mainly on clinical features in the baby and a positive HIV test in the mother. Circulating antibodies from the mother may still be present in the baby less than 18 months and hence the HIV test on the babys blood is not reliable. Pre- and post-test counseling of parents (preferably both together but at least the mother) should be done in children suspected of TB disease. 6.4. Standardized TB Case Definitions and Treatment Categories, and HIV Staging in Children: 6.4.1 Classification of TB Patients Case Definitions: In order to prescribe appropriate treatment, case definitions according to results of sputum microscopy and previous treatment are important. TB infected children are classified as in adult. 6.4.2 Diagnostic Categories Based on case definition, all TB infected children also fall into a diagnostic category for treatment, just as in adult. 6.4.3 Treatment Regimens A treatment regimen consists of two phases (As in HIV uninfected children) The initial intensive phase of fully supervised daily administration of drugs is 2 months for new cases (Cat. 1) and 3 months for re-treatment cases (Cat. 2). The continuation phase of treatment for new cases (Cat. 1) is 4 months (RH) of monthly drug collection. For re-treatment cases, the continuation phase is 5 months and should be supervised.

36

Drugs and dosages for TB treatment Treatment Regimen: Fixed dose combination for children Category 1 regimen for new cases 2RHZE/4RH (0 -14 years) Regimen Pre-treatment weight 15 - 20 8 - 14 kg <7kg kg 2 1

Intensive phase: daily supervised for 2 months Combined tablet of RHZ 3 (60mg30mg+150mg)+ Tablet Ethambutol (100mg) Continuation phase: daily for 4 months (monthly collection) Combined tablet of RH (60mg + 30mg) 3

Category 2 regimen for Relapses, Failure, Return after Default and Others 2SRHZE/1RHZE/5RHE (0 -14 years) Regimen Pre-treatment weight 15 - 20 8 - 14 kg <7kg kg Intensive phase: daily supervised for 2 months Combined tablet of RHZ 3 2 1 (60mg30mg+150mg)+ 3 Tablet Ethambutol (100mg) 0.5 gram 2 1

0.25 gram 0.25 gram

Add Injection (S) Streptomycin daily (in the first 2 months) Continuation phase: daily intake for 5 months (monthly collection) Combined tablet of RH (60mg + 30mg) 3 Tablet Ethambutol (100mg)

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Children who fail category I and II treatment should be evaluated for drug resistant TB. 6.4.4 Treatment of EPTB among HIV positive children: In general, extrapulmonary tuberculosis is treated with the same drugs as pulmonary tuberculosis. Some experts recommend extending the duration of therapy in patients with Meningeal/bone/joint tuberculosis (12 months). Corticosteroids may be useful in TB meningitis and pericarditis. 6.5.5 Antiretroviral Treatment in TB Co-infected children 6.5.5.1 HIV-positive TB patients have a much higher case-fatality during and after anti-TB treatment compared with HIV-negative patients hence the need for early introduction of ART drugs for co-infected clients. When to start to start ART in Children with TB who are co-infected with HIV: Possible Scenario GHCW should: New diagnosed TB Start/Continue children (Cat 1) TB Cat 1 with HIV positive treatment result Initiate cotrimoxazole prophylactic therapy Refer to Medical officer Medical Officer ART Regimen Continue TB Cat 1 TDF + 3TC/FTC + EFV (Preferable) treatment Continue cotrimoxazole prophylactic therapy Evaluate for ART and start ART as soon as TB treatment is tolerated (usually within 2- 8 weeks)

Children on Cat II regimen with HIV positive result

Choice of ART should take into account patient is on rifampicin during the intensive phase Start/Continue Continue TB Cat II TDF + 3TC/FTC + EFV (Preferable) TB Cat II treatment treatment Continue coInitiate cotrimoxazole trimoxazole prophylactic therapy prophylactic Start ART as soon as 38

therapy Refer to Medical officer

TB treatment is tolerated (usually within 2- 8 weeks)

Choice of ART should take into account patient is on rifampicin during the 8 months course of treatment HIV positive Refer to Medical Start TB treatment TDF + 3TC/FTC + EFV children on ART officer immediately and if (Preferable) who develops TB ART regimen contains after 6 months Nevirapine, substitute with Efavirence If clinical condition deteriorates, consider immune-reconstitution syndrome If presentation is extra pulmonary TB, this should be considered as ART failure Change to 2nd drugs 3TC or FTC +ATV/r or LPVr (if rifabutin is available). If rifabutin not available: Same NRTI as line ARV backbones recommended for adults and adolescents plus LPVr or SQV/r with super boosted dosing of RTV (LPV/r 400mg/400mg twice daily or LPV/r 800mg/200mg twice daily or SQV/r 400mg/400mg twice daily)

HIV positive Refer to Medical children on ART officer who develops EPTB after 6 months

6.5.5.2

. Drug-Drug interactions in Co-treatment of TB and HIV in children

Treatment of both TB disease and HIV at the same time is complicated by drug-drug interactions between rifampicin and the antiretroviral drug groups: non-nucleoside reverse transcriptase (NNRTIs) and protease inhibitors and (PIs). Rifampicin stimulates

39

the activity of the cytochrome P450 liver enzyme system, which metabolizes the PIs and NNRTIs. This can lead to decreased blood levels of PIs and NNRTIs. PIs and NNRTIs can also enhance or inhibit this same enzyme system, and lead to altered blood levels of rifampicin. These potential drug-drug interactions may result in ineffectiveness of ARV drugs, ineffective treatment of TB or an increased risk of drug toxicity Refer All Children with TB who are HIV positive to Medical Officer for necessary adjustments in medication TB is a preventable disease in both HIV-infected and un-infected children. 6.5.5.3 . Immune Reconstitution Syndrome (IRS) Occasionally, patients with HIV-related TB may experience a temporary exacerbation of symptoms, signs and/or radiographic manifestations of TB after beginning anti-HIV treatment. This paradoxical reaction in HIV-infected patients with TB is thought to be a result of immune reconstitution. This occurs as a result of the reactivation of the dormant immune system after the commencement of HAART especially within the first six weeks of treatment when TB is disseminated and CD4 cell counts are low. However immune reconstitution may occasionally occur after six weeks to a year. Some of the symptoms and signs may include: high fever, lymphadenopathy, expanding central nervous system lesions and Worsening of CXR findings. A thorough evaluation is necessary to exclude other causes, particularly TB treatment failure, development of other OIs or drug fever, before diagnosing a paradoxical reaction. GHCW should refer any suspected case of IRS to medical officer for appropriate management. Management of IRS: Inform patients about the possibility of an event after starting ARV; No need to stop or change TB or ARV treatment; Symptomatic treatment with non-steroidal anti-inflammatory drug (NSAID); Add steroids for severe symptoms to suppress the enhanced immune response for a short period of time; and Give short and sharp treatment of hydrocortisone or prednisolone 1 mg/kg body weight once a day for 14-21 days. Health Care worker providing care for TB patients should inform the patient

40

about the possibility of IRS before starting ARV

6.5.5.4 . Management of household child contact and contact tracing: A child under 5 years living with a sputum positive PTB patient is at high risk of TB infection and developing TB disease especially if HIV positive. Also TB suspect adult contacts identified should be further evaluated for TB. Hence all adult/children TB contacts should be screened for TB as well as counseled and tested for HIV using the chart below:

How to identify and manage child contacts of infectious adults Target group of Infectious adults Smear Positive adults

Identify all children at risk Select children for screening

Household Child Contact

All children < 5 years Other children with cough > 2 weeks

Screening

History/Examination Mantoux Chest X-ray

Outcome

TB Unlikely

TB Possible

TB highly likely

Action

IPT if less than 6 years

Treat for other possibilities and reevaluate

Confirm diagnosis

41

Register and treat for TB

All child household contacts (under 6 years of age) of sputum smear positive PTB patients should be evaluated for IPT. Dosage: 10mg/kg body weight for 6 months 6.5.5.5 . Isoniazid Prophylaxis for Children below 6 Years

Every child below 6 years of age that is living under the same roof with a smear positive patient should be brought to the health facility for examination. For symptoms of tuberculosis in children, see above Diagnosis of TB in Children. If symptoms of tuberculosis are present; o Refer to a Medical Officer who will confirm the diagnosis. o Register the patient and start treatment if diagnosis of TB is confirmed. If symptoms of tuberculosis are absent; o Give Preventative treatment after certification by the Medical Officer, regardless of whether BCG vaccination has been given in the past. o Register the patient in the Isoniazid-prophylaxis Register (NTBLCP/TB9) and o Fill the Child INH Prophylaxis Card (NTBLCP/TB8) according to the NTBLCP guidelines and Staple this card to the treatment card of the smear positive contact of the child.

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7. Prevention and Management of Opportunistic Infections.

7.1. Introduction Opportunistic infections (OIs) are infections or disease conditions that take advantage of the depressed immunity of HIV-infected persons. In Nigeria, TB is the most important OI in terms of morbidity and mortality in PLWHAs. Care givers at the PHC facility level are expected to be familiar with some of these OIs, and be able to give treatment to alleviate the symptoms using the syndromic management approach or refer cases as required. 7.2 List of common Opportunistic Infections (OI) in Nigeria The common OIs are due mainly to: viral, fungal, bacterial and parasitic/ protozoal organisms, which include tuberculosis, diarrhoea diseases (infectious),oral and vaginal candidiasis, respiratory tract infections, herpes zoster, scabies, Kaposis sarcoma, etc. Viral Herpes Simplex Herpes Zooster Multiple bluish nodules (Kaposi sarcoma) Human papilloma virus (vaginal warts) Viral upper respiratory tract infection Fungal Ringworm Nail infections Candida infections Bacterial Papulo-pruritic eruptions Pneumonia Diarrhoeal diseases Urinary tract infection TB Protozoal / Parasitic Scabies Diarrhoeal diseases Toxoplasma encephalitis See Annex 1: for table of management of OIs in Nigeria. 7.3 Isoniazid Preventive Therapy (IPT)

Isoniazid Preventive therapy (IPT) is the use of Isoniazid in HIV Positive individuals with latent TB infection and under five contacts of PTB index cases in order to prevent the development of active TB disease. Available evidence shows that TB is the commonest opportunistic infection and the leading cause of death among PLWHA and also that IPT is effective in preventing it. 43

IPT is not the treatment for active TB. It is therefore necessary to exclude active TB before commencing a patient on IPT. This therapy should be left at the discretion of a medical officer experienced in management of Tuberculosis and HIV/AIDS 7.3.1.1 Target groups for Preventive Treatment Infants of mothers with either Smear Negative or Positive PTB Children under 6 years of age HIV-infected individuals Health care workers who are HIV positive HIV positive prison inmates 7.3..2 Eligibility for IPT For a patient to benefit from IPT, he/she must: Asymptomatic HIV Positive patients Not have active TB. Be motivated to adhere to treatment. 7.3..3 Services needed before setting up a preventive therapy service Before a preventive therapy service is considered, the following prerequisites should be in place: Adequate capacity for HIV counseling, which should include IEC about TB; Sufficient trained health care staff; Linkage between HIV care and TB control services; 7.4..4 Steps in Commencing IPT The following steps should be followed before a patient is placed on IPT Verify/Confirm HIV Status Counsel on TB/HIV interactions Exclude active TB o Ask the patient about cough, chest pain, fever, night sweats and weight loss etc o Check for lymph node enlargement o Those with the above symptoms/signs should not be considered for IPT o Do sputum smear examination for AFB o Refer/commence short course chemotherapy for TB (DOTS) if smear-positive o Refer those with negative sputum smear results to medical officers for excluding active TB by chest X-ray or culture where available Commence IPT, if no active TB is confirmed

7.3..5. Dosage of INH for IPT 5mg/kg/day to a maximum of 300mg/day for six months. INH should be dispensed monthly to enhance compliance. 44

Counsel patient on: o Treatment adherence o Side-effects of INH o Immediate recognition and reporting of signs and symptoms of active TB Complete necessary INH Prophylaxis Register and complete INH Appointment Card. (See INH prophylaxis Treatment register for PLWHA and INH Prophylaxis card in the annex.)

Monitor During monthly drug refills, monitor patient o For development of active TB (clinical assessment of signs and symptoms of active TB ) o Ask for side-effects; the commonest side-effect is peripheral neuropathy (numbness/tingling sensation of extremities). If present give Pyridoxine 50-75 mg daily o Check for jaundice. If present stop IPT and refer to medical officer for assessment o Check for allergic skin eruptions Note: If patient develops signs and symptoms suggestive of active TB during the course of IPT: Discontinue IPT, Assess for active TB, Commence DOTS if confirmed or refer to medical officer. Assess for ART Cotrimoxazole Preventive Therapy (CPT)

7.4

Cotrimoxazole preventive therapy (CPT) is use of cotrimoxazole for the prevention of several secondary bacterial and parasitic infections in HIV-infected individuals. It helps to improve the quality of life and reduce the rate of death among HIV-infected patients and those that are dually infected. 7.4..1 Eligibility For a patient to benefit from CPT, he/she must be: A PLWHA with symptomatic HIV Asymptomatic PLWHA with t CD4 count of <350/mm3 Motivated to adhere to treatment A PLWHA with active TB irrespective of CD4 count A pregnant PLWHA after the first trimester A child born to an HIV-infected woman (offer CPT from six weeks of age or at first contact) A child identified as HIV-positive within the first year of life

45

7.4..2 Steps for CPT Verify HIV status Take medical history and screen for contraindications to CPT o Known allergy to sulphur containing drugs (which includes cotrimoxazole and sulphadoxine-pyrimethamine o First trimester pregnancy o Kidney or Liver disease o Seriously ill patient o Children with glucose -6- phosphate dehydrogenase deficiency Conduct physical examination Counsel patient on o OIs in HIV infection o Drug adherence o Side-effects of cotrimoxazole 1. Skin eruptions, which may be severe (Stevens Johnson syndrome) 2. Kidney or Liver failure 3. Anaemia Treat pre-existing OIs Commence CPT 2 weeks before ART commenced in eligible patients. 7.4.3 Dosage of Co-trimoxazole for CPT Adults: 960mg daily (two single strength tablets) Children: 4mg/kg body weight once daily. Cotrimoxazole syrup is preferable, in its absence, the tablets can be crushed. Monitor patients o Adult should be reviewed monthly initially, and then three monthly thereafter if the medications are tolerated o Laboratory monitoring of adults should take place every six months or when clinically indicated. This should include hemoglobin and white cell count o Children should be reviewed monthly o Replenish patients drug during review Discontinue CPT o If side-effects occur o If children test HIV-negative when older than 18 months (where CPT was commenced in infancy) o When CD4 count rises above 500 for at least 6 months( in HIV patient without TB CD4 should be above 350) Complete necessary CPT Prophylaxis Register and Treatment Appointment Card Assess for ART

8. Prevention of TB/HIV in Health Care Settings.

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8.1 Introduction From the public health point of view, the best way to prevent TB is to provide effective treatment for people with infectious TB. This interrupts the chain of transmission. Good treatment programmes are the best prevention programmes. HIV-infected individuals are particularly susceptible to infection with M. tuberculosis and the development of TB. 8.2 TB Infection Control (TB-IC) I Health care settings. Health care workers and other staff are at particularly high risk of infection with TB because of frequent exposure to patients with infectious TB disease. They may also be immune-suppressed due to HIV infection and be at higher risk of developing TB disease once infected. Persons with HIV-associated immune-suppression may become infected or re-infected with TB if they are exposed to someone with infectious TB disease. They can progress rapidly from TB infection to disease over a period of months rather than a period of years as is common for persons with a normal immune system. Long waiting hours as well as overcrowding and poor ventilation of health facilities increase the risk of TB transmission among clients receiving care and portraying danger to health workers delivering care. This section highlight steps to reduce TB-IC in health care settings, refer to National Guidelines on TB infection control for detail information. 8.3 Interventions to reduce risk of infection There are three main ways in which the risk of Tuberculosis infection can be reduced. Work practice and administrative control measures Environmental control measures Personal protective measures In all, work practice and administration control measures have the greatest impact on preventing TB transmission. Environmental control measures provide further steps to reduce/eliminate risk of exposure. 8.3.1 Work Practice and Administrative Control Measures These serve as the first line of defence for preventing the spread of TB in HIV settings. The aims are : To prevent TB exposure to staff and patients To reduce the spread of infection by ensuring rapid and recommended diagnostic investigation and treatment for patients and staff known to have TB. These can best be accomplished through the prompt recognition, separation, provision of services, and referral of persons with potentially infectious TB disease. 8.3.3.1 Recommended TB-IC procedures at General Out-patient Departments HIV-positive patients and staff in health units face daily exposure to TB. The following procedures are suggested: Ensure prompt diagnosis and treatment of patients with sputum smear-positive PTB

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Ensure prompt outpatient diagnosis and treatment of PTB patients to prevent hospital admission. In-patient management of intensive phase TB patients should as much as possible be avoided. Known HIV-positive health workers should not work with PTB patients (they should therefore not work in TB wards or adult medical wards) Ensure good ventilation to help reduce TB transmission indoors. Wards should have large windows as sunlight is a source of ultraviolet light, which can kill TB bacilli. Laboratories that process sputum specimens for AFB should follow should follow standard operating procedures involved in good laboratory practice (GLP). In wards, outpatient clinics, sputum collection rooms, microbiology laboratories, surgical and autopsy suites, keep the doors closed and the windows open. Educating the TB suspects and TB patients on Dangers of Exposure and Prevention covering the mouth with a clean handkerchief/cloth when coughing/sneezing, and using sputum pots with lids. When examining TB patients or suspects, ask them to turn their head away, to avoid coughing directly at the health worker. Wet floor before sweeping (bleach should be used rather than disinfectants like Izal, Dettol etc.)

8.3.3.2 Recommended procedures for TB-IC in the Medical Wards If possible admit them to a separate ward from other patients. If there are no facilities to separate PTB suspects from other patients, at least try to keep PTB suspects in a part of the ward away from other patients. Staff should also encourage PTB suspects to spend daylight hours outside the ward if the weather is good. Sputum for smear examination should be collected as rapidly as possible. The laboratory should process and examine sputum smears rapidly and efficiently. Hospitals should ensure a minimum of delay in delivering smear examination results back to the wards. Children should be discouraged to accompany infected adults for DOTS follow-up and from entering TB inpatient wards/clinics for social visits 8.3.3.3 The TB infection control plan for all health facilities

Ideally, each facility should have a written TB infection control plan which outlines a protocol for the prompt recognition, separation, provision of services, investigation for TB and referral of patients with suspected or confirmed TB disease. Screening all clients to identify persons with cough > 2 weeks as soon as possible after arrival at the facility Asking patients to cover their mouths when they cough if possible Placing TB suspects in a separate well-ventilated waiting area or outside

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Suggested clinic operating procedure: A staff person should direct or escort the TB suspect to a separate waiting area. Clients need to be assured of their place in the queue for registration and/or services. (This special waiting area should have the highest natural ventilation possible.) Expediting TB suspects receipt of services in the facility Suggested clinic operating procedure: TB suspects should be moved to the front of the queue for whatever services they are accessing, e.g., HIV testing and counseling or VCT, medication refills, medical evaluation. This reduces the duration of potential exposure in the facility and may be an incentive to disclose information during screening. Ensuring rapid investigation of TB suspects or referring TB suspects to TB diagnostic services if not available on site. Using and maintain environmental control measures (see next section) Screening of staff for symptoms of TB disease (see Section A) Providing voluntary, confidential HIV counseling and testing for staff with appropriate access to treatment Training and educating all staff on TB, TB control and the TB infection control plan. Monitoring the implementation of the TB infection control plan

8.3.4 Environmental control measures Environmental controls are the second line of defense for preventing the spread of TB in HIV care settings. If the work practice controls are inadequate, environmental controls will not eliminate the risk of spread of TB. Environmental control measures include: 8.3.4.1 Ventilation (natural and mechanical) Controlled natural ventilation can reduce the risk of spreading TB. Ventilation is the movement of air in a building and replacement of air in a building with air from outside. When fresh air enters a room it dilutes the concentration of particles, such as droplet nuclei containing M.tb, in room air. Open doors and windows to bring in air from the outside; controlled implies that checks are in place to make sure that doors and windows are maintained in the position that enhances ventilation. Design waiting areas and examination rooms so that they have maximum natural ventilation can help reduce the spread of TB. Always collect sputum for TB outside (open environment) and away from other people, not in small rooms such as toilets or other enclosed areas. .

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8.3.4.1

Protection of health workers

The primary way to prevent transmission of TB to health workers and others at the health facility is for TB patients to take their drugs regularly. They will then become non-infectious in a week or two. Good ventilation of the place where treatment is provided is also very important. Personal respiratory protection (respirators) are not a priority intervention. Respirators can protect health care workers from inhaling M. tb only if appropriate work practice and environmental controls are in place; i.e., they are a last line of defense. They are expensive to purchase and require specialized equipment to determine the appropriate fit. Frequently, they are unavailable in resource-limited settings. Their use should be restricted to specific high risk areas in hospitals and referral centers, such as rooms where spirometry or bronchoscopy are performed or specialized treatment centers for persons with multi-drug resistant TB. Respirators are different from face masks, such as surgical masks made of cloth or paper. Face masks do not protect those wearing them from inhaling M. tb. In fact, the use of these masks may contribute to a false sense of security. There is no role for health care workers or staff to use face masks for protection from TB. 8.4 Prevention of HIV transmission in Health care settings Less than 0.5 % of health workers exposed to a needle-stick injury from the blood of an HIV-positive patient have acquired HIV infection. The following are recommended precautions for healthcare workers Assume that all blood and body fluids are potentially infectious Handle all sharps (needles and syringes) carefully and discard used ones into a disposable container, then burn them. If you have a needle-stick injury, squeeze the wound to encourage blood flow and wash well with soap and water and follow the steps outlined below under PEP. The table below gives some guidance on prevention of transmission to health workers. Table 11.1: Precautions for Healthcare Workers against Occupational Risks

Exposure to risk Venepuncture

Precaution for prevention of transmission of HIV Wear gloves Use a closed vacuum system if available Discard needle and syringe into sharps box Discard gloves and swabs into leak-proof plastic bag for incineration (burning) Label blood bottle and request form inoculation risk

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 Invasive procedure, surgery or delivery of a baby Spilled blood Resuscitation 8.5

Wear gloves and apron Protect your eyes (glasses or protective goggles) Discard sharps into sharps box Clean up as soon as possible using available disinfectant (e.g. Dettol, Purit, Savlon, Izal) Avoid mouth-to-mouth resuscitation (use Ambu-bag)

Guidelines for Post Exposure Prophylaxis (PEP) for HIV

8.5.1 Introduction and rationale of PEP Information about primary HIV infection indicates that systemic infection does not occur immediately after exposure, leaving a brief window of opportunity during which administration of PEP might prevent viral transmission and replication. Commencement of PEP within two hours after exposure might inhibit or prevent systemic infection. After an exposure the following steps should be pursued: 8.5..2 First aid Following any occupational exposure, the following are recommended before reporting: 1. Wash percutaneous injuries with soap under running water (tap or stored water) and allow the wound to bleed freely; do not compress to stop bleeding. 2. Use water to flush out nose, mouth or areas of the skin (broken) that have been splashed with blood. 3. Irrigate eyes when exposed with saline or clean water 4. Report and document incident immediately through supervising officer. 5. Index worker and supervisor should consult an expert or the designated persons listed immediately or be immediately referred to an ART treatment center for PEP. 8.5.3 Evaluate exposure risk assessment Low risk Solid needle injury Superficial sharps injuries Exposure to blood/fluid from asymptomatic HIV patient with low viral load or suppressed viral load on therapy Exposure to a small amount of infected blood/fluid Splash of blood on intact skin High risk Deep injury with hollow especially large bore needle Exposure to blood/fluids of patient with AIDS or advanced HIV infection or acute seroconversion illness Extensive and deep sharp injury Exposure to large volume of infected blood / fluid 51

 Splash of blood on broken skin 8.5.4 Evaluation of exposure source Known Source Enquire whether patient is known to be infected with HIV Evaluate HIV infected patients stage, performance status, CD4 cell count (or lymphocyte counts) and clinical condition If status unknown, test for HBsAg, HCV and HIV antibodies using rapid HIV testing technique with informed consent. [Screening for HIV should not be delayed or deferred to await HBV and HCV screening] If source is not infected with any of the above viruses, baseline testing or further follow-up is not necessary (unless strong suspicion or possibility that he / she is in the window period should especially suspect sexually active individuals). If source person refuses testing, consider clinical presentation, diagnoses and history of risk behaviors; consider source infected if sexually active. Unknown Source Evaluate the likelihood of exposure to a source at high risk for infection Consider the likelihood of infection among patients in the exposure setting

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ANNEX:
Annex 1: Adverse Drug Reporting Form:

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Annex 2: Organ Involvement

Management of Common OIs in Nigeria Complaints Itchy Rash Examination findings Papular rash and pustules located mainly on the extensor surfaces of the arms, back of the hands, and trunk; there is sparing of the palms and soles. The condition is chronic and tends to wax and wanes. Scratch marks may or not be present Papular rash more on the webs of the fingers and toes often with scratch marks Clinical Judgment Papulopruritic eruptions Action Reassure Treat with antihistamines e.g. Antisan cream Tab piriton 1 tds x 1 week If no improvement refer

SKIN

Scabies

Painful rash

Painful fluid filled skin rash with a reddish base on one side of the body not crossing the midline Painful rash/ blisters on the lips and tips of the penis or vulva Multiple bluish purple rashes commonly found at the back of the hand and at the dorsum of the foot. Itchy scaly lesions

Benzyl benzoic acid solution, apply topically bd from neck downwards x 4 days. Herpes Reassure the Zoster patient. Paracetamol 1000mg qds x 3days Ascorbic acid 100mg daily x 7 days Zovirax cream topically. Tab acyclovir 200mg tds x 2 weeks Refer if no improvement. Ring worm Apply Whitfield

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spreading at the edges on any part of the body

ORAL PHARNGEAL LESIONS.

Pain in the throat Fever Pain on swallowi ng Altered taste.

GASTRO INTESTINAL SYSTEM

Frequen t watery stools more than 5 times daily Abdomi nal cramps weakness

,clotrimazole or Miconazole ointment twice daily. Continue for one month extra after disappearance of lesions Refer if no improvement. White patches in Oral Reassure pharyngeal the mouth cavity patient thrush Palpable Nystatine enlarged lymph oral nodes suspension ( to confirm dosage) and Gentian violet paint for 14 days Paracetamol 2 tabs. tds. x 3days. Tab. Clotrimazole 10mg 5 times x 2 weeks. Fluconazole 200mg daily 2 wks bacterial / fluid watery stools parasitic replacement dehydration infections (ORS) Tab. Cotrimoxazo le 960mg bd x 5 days and / or Tab. Metronidazo le 400mg tds x 5 days Refer if symptoms persist

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UROGENITAL SYSTEM

SYSTEMIC INFECTIONS

Persistent diarrhoea for 14 days with weight loss Recurrent or persistent diarrhoea for more than one month. Abnorm al vaginal discharg e Male urethera l discharg e Genital ulcers Groin swelling Female lower abdomin al pain Scrotal swelling. Fever, Malaria Weakne ss Chills Rigours Headach e Joint pains

Evidence weight loss. Dehydration Marked weight loss

of Unexplaine d diarrhea

Give ORS in sips and refer.

Unexplaine Refer d diarrhoea immediately to medical officer.

Refer to the Guidelines on STI on syndromic management of STI

Treat as in the Guidelines for syndromic management of STI.

Febrile Parlour

Screen for malaria and Enteric fever and treat accordingly.

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RESPIRATOR Y TRACT INFECTION

Viral upper Clear respiratory nasal tract discharg infection. e Headach e Malaise Slight Fever Upper respirat ory tract infection Severe Cough cough lower productive Chest respiratory sputum pain drawing of tract Difficult In infection intercostals space y in ?Pneumoni breathin a g malaise

Paracetamol 2 tabs. bd x 3 days Piriton 1 bd x 3 days Multivitamin s tabs 1 tds x 2 weeks. Vitamin C 2 tds x 2 weeks

Bed rest Good diet Give paracetamol and consider referral if condition persists

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Annex 3: Rifabutin Use in HIV/TB Co-infection SOP for Rifabutin Use in HIV/TB Co-infected Patients Requiring Protease InhibitorBased Antiretroviral Therapy 1. Introduction: Use of rifampicin with standard doses of protease inhibitors (PI) is not recommended due to a significant reduction in blood levels of PIs, risking virologic failure. Although adjusted doses of lopinavir/ritonavir may overcome this interaction, there is concern for higher rates of gastrointestinal intolerability or hepatotoxicity. Therefore, rifabutin is preferred to rifampicin in HIV/TB co-infected patients requiring PIbased antiretroviral therapy (ART). Rifabutin has comparable efficacy to rifampicin and is well-tolerated, but does not significantly reduce the blood levels of ritonavir-boosted PIs. However, the ritonavir-boosted PI significantly increases blood levels of rifabutin; therefore, when co-administered, rifabutin must be given at a lower than standard dose. Based on the available evidence to-date, the recommended rifabutin dose in adults when given in combination with ritonavir-boosted PIs is rifabutin 150 mg every two days (instead of standard doses of 300 mg once daily). PI dose adjustments are not required when given with rifabutin. Rifabutin should only be used among persons living with HIV(PLHIV) who require PIbased ART and anti-TB drugs 2. 2.1. Drug Tables: ADULTS

Category 1 Regimen for New Cases (6months regimen): 2RfbHZE/ 4RfbH Regimen Pre-treatment weight Intensive phase: daily supervised for 2 months > 55 kg 40 55 kg 21-39 kg (Rfb) Rifabutin 150 mg EVERY 2 DAYS Combined tablet of EH(400mg + 150mg) Daily (Z) Pyrazinamide 400 mg Daily Continuation phase: daily supervised RfbH for 4 months (Rfb) Rifabutin 150mg EVERY 2 DAYS 1 1 1 1 2 4 1 2 3 1 1 2

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(H) Isoniazid 100mg Daily

Category 2 Regimen for Relapses, Failures, RAD and Others: 2SRfbHZE/RfbHZE/5(RfbHE) Regimen Pre-treatment weight Intensive phase: daily supervised for 3 months > 55 kg 40 - 55 kg 25-39 kg (Rfb) Rifabutin 150mg EVERY 2 DAYS Combined tablet of EH(400mg + 150mg) Daily (Z) Pyrazinamide 400 mg Daily Add in the first two months daily: (S) Streptomycin Continuation phase daily supervised for 5 months (Rfb) Rifabutin 150mg EVERY 2 DAYS Combined tablet of EH(400mg + 150mg) Daily 1 2 4 1 2 3 1 1 2

1 gram 1 2

0.75 gram 0.5 gram 1 2 1 1

Streptomycin should NOT be given to pregnant women. Patients >45 years should not be given more than 0.75g of streptomycin irrespective of weight Use of rifabutin in HIV/TB co-infected pregnant women on PI-based ARVs: For pregnant women requiring the use of ritonavir-boosted PI-based ART or PMTCT and anti-TB therapy, change rifampicin to rifabutin. Dosing of rifabutin during pregnancy should follow the recommendations outlined above. 2.2. CHILDREN (0-14 YEARS)

Category 1 Regimen for New Cases: 2RfbHZ+E/4RfbH Regimen Pre-treatment weight Intensive phase: daily supervised for 2 months 15-20 kg 8-14 kg 5-7 kg (H) Isoniazid 100 mg 2 1 1

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(Rfb) Rifabutin* (Z) Pyrazinamide 400 mg (E) Ethambutol 100mg Continuation phase: daily supervised for 6 months (Rfb) Rifabutin* (H) Isoniazid 100 mg 2 1 1 1 3 1 2 1

Category 2 Regimen for Relapses, Failures, RAD and Others: 2RfbHZ+E/RfbHZ+E/5RfbH+E Regimen Pre-treatment weight Intensive phase: daily supervised for 3 months 21-33 kg 11-20 kg 5-10 kg (H) Isoniazid 100 mg (Rfb) Rifabutin* (Z) Pyrazinamide 400 mg (E) Ethambutol 100mg (S) Streptomycin Continuation phase: daily supervised for 5 months (H) Isoniazid 100 mg (Rfb) Rifabutin* (E) Ethambutol 100mg 3 2 1 2 1 1 1 3 0.5gram 1 2 0.25mg 1 0.25mg 2 1 1

Rifabutin dosage in children

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Children < 1 year: 2.5mg/kg body weight given daily Children > 1 year: 5mg/kg body weight given daily

* Rifabutin (Rfb) is available in capsule form and has to be compounded when required in children, usually by a pharmacist in a specialized centre. 3. Adverse Events/Toxicity of Rifabutin Abdominal pain Bloating Chest pain Taste perversion Headache Discolouration of body fluids, giving a red-orange or red-brown colour to urine, faeces, saliva, skin, sweat, and tears Allergic reactions, including skin rash and itching GI effects, including anorexia, diarrhoea, dyspepsia, nausea, and vomiting Haematologic abnormalities, including anaemia, leukopenia, neutropenia, and thrombocytopenia. Uveitis characterized by itching, decreased vision, photophobia, pain, and temporary blindness in some patients. Patients with uveitis should be referred to ophthalmologist Among this group of patients on ARVs and Rfb containing anti-TB drugs, the side effects may be similar or may potentiate each other. Therefore, when side effects occur, refer the patient to a Medical officer. Note: Rifabutin decrease the efficacy of oral contraceptives that contain estrogen by inducing the hepatic metabolism of estrogen. Patients using oral contraceptives should consider

changing to nonhormonal methods of birth control.

Rifabutin is metabolized through CYP3A enzymes, inhibitors of these enzymes, such as fluconazole or clarithromycin, may increase rifabutin plasma concentrations. The dosage of rifabutin may need to be reduced. In cases of severe renal impairment (creatinine clearance less than 30 mil/min), the dosage of rifabutin may also need to be reduced.

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Annex 4: Clinical Staging of HIV/AIDS infection: PLHIV with pulmonary TB are in clinical stage 3 of HIV infection while those with Extrapulmonary TB are in stage 4 of HIV infection
Clinical Stage 1 Asymptomatic Generalized lymphadenopathy Performance scale 1: asymptomatic, normal activity Clinical Stage 2 Weight loss, <10% of body weight Minor mucocutaneous manifestations (seborrheic dermatitis, fungal nail infections, recurrent oral ulcerations and angular chelitis) Herpes zoster within the last five year Recurrent upper respiratory tract infection (i.e. bacterial sinusitis) And/or performance scale 2: symptomatic, normal activity Clinical Stage 3 Weight loss > 10% of body weight Unexplained chronic diarrhoea > 1 month Oral candidiasis (thrush) Oral hairy leukoplakia Pulmonary tuberculosis within the past year Severe bacterial infections (i.e. pneumonia, pyomyositis) And/or performance scale 3: bedridden <50% of the day during last month Clinical Stage 4 HIV wasting syndrome Peumocystis Carinii Pneumonia Toxoplasmosis of the brain Cryptococcus, extrapulmonary Cytomegalovirus disease of an organ other than liver, spleen or lymph node e.g retinitis Herpes simplex virus infection, mucocutaneous (>1 month) or visceral Progressive multifocal leucoencephalopathy Any disseminated endemic mycosis Candidiasis of esophagus, trachea and bronchi Lymphoma Kaposis sarcoma HIV encephalopathy Extrapulmonary tuberculosis And/or performance scale 4: bedridden>50% of the day during last month *Assessment of body weight in pregnant women need to consider expected weight gain of pregnancy
Unexpected refer to those conditions whose presence is not explained by other conditions

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