HIV ASSOCIATED TUBERCULOSIS OF PEOPLE IN DEVELOPING COUNTRIES

ALI AUFAR HUTASUHUT 030.09.008

Faculty o !"#$c$%" TRISA&TI UNIVERSIT' (a)a*ta +0,+

ABSTRACT The association between tuberculosis and HIV presents an immediate and grave public health and socioeconomic threat, particularly in the developing world. In early 1992 WH estimated that appro!imately " million people had been in#ected with

both Mycobacterium tuberculosis and HIV since the beginning o# the pandemic$ 9%& o# them were in developing countries. The association between tuberculosis and HIV is evident #rom the high incidence o# tuberculosis, estimated at %'(& per year, among HIV)in#ected persons, the high HIV seroprevalence among patients with tuberculosis, the high occurrence o# tuberculosis among *I+, patients, and the coincidence o# increased tuberculosis noti#ications with the spreading o# the HIV epidemic in several *#rican countries. The impact o# the two epidemics on resource)poor countries has ominous social and medical implications, and the already overstretched health services now have to #ace a tremendously increasing tuberculosis problem. HIV in#ection worsens the tuberculosis situation by increasing reactivation o# latent tuberculosis in#ection in dually in#ected persons as well as by #avouring rapid progression o# new in#ections in the HIV)in#ected. This also results in an increase o# the ris- o# in#ection and a subse.uent increase o# cases in the general population. In order to respond to this urgent problem, the highest priority must be given to strengthening tuberculosis control programmes in the countries where they are poorly developed and where the prevalence o# HIV and tuberculosis in#ections is high. /esides improving the cure rate by early diagnosis and prompt treatment o# patients with tuberculosis, two ma0or strategies that need consideration include /12 vaccination and preventive chemotherapy among HIV)in#ected individuals. The latter strategy is considered as

the most critical intervention that would help to limit the e!pected increase in clinical tuberculosis #rom the pool o# HIV and tuberculosis coin#ected individuals. However, a number o# issues need to be addressed urgently and be#ore such an intervention can be implemented in the developing countries.

CHAPTER , INTRODUCTION

,., Bac)-*ou%# Tuberculosis is one o# many worldwide public health problems. 2lobally Tuberculosis remains among the leading causes o# death #rom an in#ectious agent. In 233(, the estimated global T/ incidence rate was 149 cases per 133,333 populations, which e.uates to 9." million 5range, (.9'9.9 million6 incident T/ cases 516 ,ome people who had immunode#iciency state because o# HIV can be easily in#ected by 7ycobacterium Tuberculosis because their body can not protect the body itsel# #rom the antigens, so globally, 43& o# HIV)in#ected persons are estimated to have concomitant 5usually latent6 in#ection with 7. tuberculosis.516 The clinical presentation o# pulmonary tuberculosis can vary widely in both immunocompetent and immunocompromised hosts. In general, the presentation in the HIV) in#ected patient is similar to that seen in HIV)unin#ected patients, although the signs and symptoms 5such as #evers, weight loss, and malaise6 may be attributed to HIV itsel# and the possibility o# tuberculosis overloo-ed. ,ymptoms are usually present #or wee-s to months, and the acute onset o# #ever and cough is more suggestive o# a nonmycobacterial pulmonary process 546

,.+ P*o.l"/ The important problem that will be presented is tuberculosis patient with HIV in developing countries because it has been a worldwide problem The people who is su##ering #rom HIV is easily can be in#ected by mycobacterium tuberculosis and Tuberculosis remains among the leading causes o# death #rom an in#ectious agent o# peoples in developing countries ,.3 L$/$tat$o% o P*o.l"/ 7y paper is limited in terms o# determines and the pathophysiological mechanisms that may e!plain the association between HIV and Tuberculosis. 7any #actors which can ma-e HIV, Tuberculosis, and HIV associated Tuberculosis. In this case di##erences in the pathophysiological point o# view that will be raised and discussed by the author. 7any in#ectious diseases associated to HIV because the decreasing o# antibody #unction that may lead a lot o# in#ection to this person and this antigens may attac- the target organs such as 7ycobacterium Tuberculosis which lead this person may have pulmonal Tuberculosis disease and all concerned will be discussed in this paper. ,.0 Pu*1o2" The purpose o# this paper is to #ind out more detail and discuss the determine #actors o# both diseases in a variety o# viewpoints. ,.3 !"t4o# o 5*$t$%The method is a review o# the literature. *uthor see- re#erences #rom medical 0ournals and the articles, which are related to this topic. *uthor o# the re#erence tools o# the internet. In the conte!t o# the source, the author #ound the source o# which was published less than ten years.

Tools the author o# several medical sites and some sites that have lin-s with this topic. Then, the author mades review o# re#erences. In the end, the author ma-es conclusions #rom the opinions o# this paper ,.6 F*a/" o 5*$t$%This paper contents #ive chapters. 1hapter 1 is about introduction. It is include bac-ground, problems, limitation o# problems, purpose, method o# writing and #rame o# writing. In chapter 2, writer will tal- about Tuberculosis and HIV which is include de#inition, etiology, epidemiology and the others. In addition, the authors will also e!plain about how to wor- up Tuberculosis associated HIV patients. 1hapter 4 is that e!plain the correlation between HIV and Tuberculosis in developing countries. The conclusion will be discussed in chapter "

CHAPTER + LITERATURE REVIE5

+., Hu/a% I//u%o#" $c$"%cy V$*u2 +.,., D" $%$t$o%

Human immunode#iciency virus 5HIV6 is a blood)borne, se!ually transmissible virus 5see the image below.6 The virus is typically transmitted via se!ual intercourse, shared intravenous drug paraphernalia, and mother)to)child transmission 57T1T6, which can occur during the birth process or during breast#eeding. Two distinct species o# HIV 5HIV)1 and HIV)26 have been identi#ied, and each is composed o# multiple subtypes, or clades. *ll clades o# HIV)1 tend to cause similar disease, but the global distribution o# the clades di##ers. This may have implications on any #uture vaccine, as the / clade, which is predominant in the developed world 5where the large pharmaceutical companies are located6, is rarely #ound in the developing countries that are more severely a##ected by the disease. HIV)1 probably originated #rom one or more cross)species trans#ers #rom chimpan8ees in central *#rica.91: HIV)2 is closely related to viruses that in#ect sooty mangabeys in western *#rica.92: 2enetically, HIV)1 and HIV)2 are super#icially similar, but each contains uni.ue genes and its own distinct replication process. HIV)2 carries a slightly lower ris- o# transmission, and HIV)2 in#ection tends to progress more slowly to ac.uired immune de#iciency syndrome 5*I+,6. This may be due to a less)aggressive in#ection rather than a speci#ic property o# the virus itsel#. ;ersons in#ected with HIV)2 tend to have a lower viral

load than people with HIV)1 , and a greater viral load is associated with more rapid progression to *I+, in HIV)1 in#ections. HIV)2 is rare in the developed world. +.,.+ Et$olo-y

HIV disease is caused by in#ection with HIV)1 or HIV)2, both o# which cause very similar conditions. They di##er in transmission and progression ris-s. +.,.3 E1$#"/$olo-y

*ccording to the <oint =nited >ations ;rogramme on HIV?*I+, 5=>*I+,6,9@A: worldwide in 233( appro!imately 44." million people 51& o# the global adult population aged 1%)"9 y6 were in#ected with HIV, a decline #rom 233@ 549.% million reported at that time6. =>*I+, estimates that 2.A million people were newly in#ected with HIV and that 2 million people died #rom *I+, in 233(, both statistics showing a slight decline over time. The vast ma0ority o# in#ections remain in sub),aharan *#rica, where %.2& o# the population is thought to be in#ected. /etween 233" and 233@, the prevalence o# HIV in#ection in central and eastern *sia and Bastern Burope increased by 21&. +uring this period, the number o# new HIV in#ections in persons aged 1% to @" years rose by A3& in Bastern Burope and central *sia. +.+ Tu."*culo2$2 +.+., D" $%$t$o%

Tuberculosis 5T/6, a multisystemic disease with myriad presentations and mani#estations, is the most common cause o# in#ectious disease'related mortality worldwide. The World Health rgani8ation 5WH 6 has estimated that 2 billion people have latent T/ and that globally, in 2339, the disease -illed 1.A million people. Mycobacterium tuberculosis, a tubercle bacillus, is the causative agent o# Tuberculosis.

+.+.+

Et$olo-y

7 tuberculosis is a slow)growing, obligate aerobe and a #acultative, intracellular parasite. The organism grows in parallel groups called cords 5as seen in the image below6. It retains many stains a#ter decoloration with acid)alcohol, which is the basis o# acid)#ast stains. +.+.3 E1$#"/$olo-y

2lobally, more than 1 in 4 individuals is in#ected with tubercle bacillus. *n estimated 9.2A million incident T/ cases were reported internationally in 233A, an increase #rom 9.2" million in 233@. However, although the total number o# cases increased, the number o# cases per capita decreased #rom a global pea- o# 1"2 cases per 133,333 in 233" to 149 cases per 133,333 in 233A. 1ountries with the highest prevalence include Cussia, India, /angladesh, ;a-istan, Indonesia, ;hilippines, Vietnam, Dorea, 1hina, Tibet, Hong Dong, Bgypt, most sub),aharan *#rican countries, /ra8il, 7e!ico, /olivia, ;eru, 1olombia, +ominican Cepublic, Bcuador, ;uerto Cico, Bl ,alvador, >icaragua, Haiti, Honduras, and areas undergoing civil war. The prevalence o# T/ in countries in Bastern Burope is intermediate. The prevalence o# T/ is lowest in 1osta Cica, western and northern Burope, the =nited ,tates, 1anada, Israel, and most countries in the 1aribbean. *#rica, which is home to 14& o# the worldEs population and 14 o# the 1% countries with the highest T/ incidence, shoulders over 2%& o# the annual global T/ burden in terms o# cases and deaths.

CHAPTER 3 DISCUSSION When the immune system is damaged enough that signi#icant opportunistic in#ections begin to develop, the person is considered to have *I+,. For surveillance purposes in the =nited ,tates, a 1+"G T)cell count less than 233?HI is also used as a measure to diagnose *I+,, although some opportunistic in#ections develop when 1+"G T)cell counts are higher than 233?HI, and some people with 1+" counts under 233?HI may remain relatively healthy. 7any opportunistic in#ections and conditions are used to mar- when HIV in#ection has progressed to *I+,. The general #re.uency o# these in#ections and conditions varies #rom rare to common, but all are uncommon or mild in immunocompetent persons. When one o# these is unusually severe or #re.uent in a person in#ected with HIV and no other causes #or immune suppression can be #ound, *I+, can be diagnosed5"6 Bven a#ter starting therapy and with e##ective suppression o# viral load, patients with persistently low 1+" counts remain at high ris- #or opportunistic in#ections. In general, all patients remain at a relatively high ris- #or opportunistic in#ections and other *I+,)related events #or the #irst @ months o# antiretroviral therapy. 5"6 *n observational study o# 23,A43 HIV patients in =ganda #ound that, among patients with more than si! months o# #ollow)up a#ter the initiation o# antiretroviral therapy, the pre)therapy 1+" count was still predictive o# mortality.5"6 The World Health rgani8ation 5WH 6 estimates that one)third o# the worldEs population is in#ected with 7ycobacterium tuberculosis, resulting in an estimated ( million new cases o#

tuberculosis and nearly 2 million deaths each year. *ppro!imately 13 million people are estimated to be coin#ected with 7 tuberculosis and HIV, and over 93& o# these dually in#ected individuals reside in developing nations. In some areas o# sub),aharan *#rica, the rates o# coin#ection e!ceed 1,333 per 133,333 population516. Worldwide, tuberculosis is the most common cause o# death among patients with *I+,, -illing 1 o# every 4 patients. 516 /y the end o# 233(, an estimated 44.2 million persons were in#ected with HIV, o# whom 2.1 million were children. ,imilarly, an estimated 2.A million persons were newly in#ected with HIV in 233A, and 2.1 million died o# *I+,. *ppro!imately two)thirds o# all persons in#ected with HIV live in sub),aharan *#rica . The ma0ority o# HIV)in#ected persons do not -now their HIV status, and there are no comparable global data to e!actly .uanti#y the proportion o# the population that -nows their HIV status. However, there has recently been substantial e!pansion o# HIV testing services in many countries. 1omparable data provided to the WH #rom 1A countries showed that the number o# HIV testing #acilities increased by 2.% #old between 233@ and 233A. *lthough variable with a wide range, several studies showed that only 1 o# % persons -nows his or her HIV status in many settings with a high prevalence o# HIV in#ection ;reventing HIV in#ectionJ ;revention o# HIV in#ection, the most potent ris- #actor, is essential to prevent the devastating impact on tuberculosis. The strategy calls #or support and care #or those who have been in#ected with HIV, whether they are still healthy or have developed illnesses associated with their in#ection, including *I+,. The support and care o# HIV)in#ected persons is not only humane, it is vital #or the success o# prevention. The ma0ority, up to (%)93 per cent o# all in#ections result through se!ual transmission o# HIV and an additional % per cent by in0ecting drug use$ changing se!ual and in0ecting behaviour is thus the prime #ocus o# action #or interrupting transmission. *ction #or prevention o# HIV transmission must includeJ 5i6 in#ormation and education aimed at all men and women, particularly those at high ris- o# in#ection, including se! wor-ers and in0ecting drug users health and social services especially #or the purpose o# providing condoms, clean needles and

syringes to reduce harm, and the early diagnosis and treatment o# se!ually transmitted in#ections using syndromic approach and creating an enabling environment, in the absence o# stigma and discrimination directed against people living with HIV?*I+, or those at ris-. This should be lin-ed with strategies aimed #or the social and economic empowerment o# women, and reducing the vulnerability o# young people by providing accurate in#ormation about HIV transmission to preadolescent and adolescent girls and boys, and enabling them to learn and practice the related prevention s-ills. 5"6 HIV)seropositive patients with tuberculosis respond well to antituberculosis therapy, as long as the regimen contains I>H and a ri#amycin. The treatment o# HIV)related tuberculosis re.uires close monitoring because o# #re.uent drug to!icities, possible drug)drug interactions, and parado!ical reactions. There have been si! prospective studies, #our randomi8ed and two observational in nature, o# @)month treatment regimens #or active tuberculosis 5Table 26.5%2)%A6 /ecause these studies di##ered in design, patient population, eligibility criteria, site o# disease, #re.uency o# dosing, dose administration, and outcome de#initions, it is di##icult to provide meaning#ul cross)study comparisons. It is important to note, however, that all o# the studies reported a good, early clinical response to therapy, and the time in which 7 tuberculosis sputum cultures converted #rom positive to negative and treatment #ailure rates were similar to those in patients without HIV in#ection. The recurrence rates vary between studies. *lthough most studies reported recurrence rates o# %& or less among HIV)in#ected cases, two studies reported rates close to 13&. In Dinshasa, Kaire, patients with tuberculosis were treated with I>H, ri#ampin, pyra8inamide, and ethambutol daily #or 2 months, #ollowed by I>H and ri#ampin twice wee-ly #or " months.5%26 nly one)hal# o# the doses in the continuation phase were directly observed. The HIV) seropositive cases were then randomi8ed to receive an additional @ months o# placebo or twice)wee-ly I>H and ri#ampin. There was no statistically signi#icant di##erence in the

recurrence rates between the HIV)seropositive 59&6 and )seronegative sub0ects 5%.4&6. HIV) seropositive cases who received the e!tended therapy had a recurrence rate o# 1.9& compared with 9& in the placebo group 5p L .316. +espite a lower recurrence rate in the HIV seropositive sub0ects who received e!tended therapy, there was no di##erence in survival compared with those who did not receive the e!tended treatment. The reasons #or the higher recurrence rate in the HIV seropositive patients is un-nown, but may have been because o# nonadherence in the continuation phase or e!ogenous rein#ection. The Tuberculosis Trials 1onsortium, sponsored by the 1+1, conducted a randomi8ed trial o# ri#apentine versus ri#ampin in the continuation phase o# therapy.5%A6 *dults who had completed a 2)month induction phase o# I>H, ri#ampin, pyra8inamide, and ethambutol were randomly assigned to receive 933 mg I>H and @33 mg ri#ampin twice wee-ly, or 933 mg I>H and @33 mg ri#apentine once wee-ly. ,eventy)one HIV)in#ected patients were enrolled, o# whom @1 completed therapy and were assessed #or relapse. Five o# 43 51A&6 patients in the once)wee-ly I>H?ri#apentine arm relapsed, compared with three o# 41 513&6 patients in the twice)wee-ly I>H?ri#ampin arm. Four o# the #ive relapses in the once)wee-ly group had monoresistance to ri#ampin, compared with none in the standard treatment arm. Bnrollment o# HIV)in#ected patients with tuberculosis was halted in the study because o# these #indings. The authors concluded that HIV)in#ected patients with tuberculosis should not be treated with a once)wee-ly I>H and ri#apentine regimen. In another Tuberculosis Trials 1onsortium study, an intermittent ri#abutin)based regimen was evaluated. This was a single)arm trial o# twice) wee-ly ri#abutin)based therapy in HIV)in#ected persons. Five patients who #ailed treatment or relapsed developed ac.uired ri#amycin resistance. *ll #ive had low 1+" counts 5L@3 cells?mm46. Four received twice)wee-ly therapy in the #irst 2 months o# treatment, and all #ive received twice)wee-ly therapy in the continuation phase. /ased on these #indings, #or HIV)in#ected persons with 1+" counts L133 cells?mm4, daily therapy is indicated during the #irst 2 months, #ollowed by either daily therapy or three doses per wee- during the continuation phase. 5%6

CHAPTER 0 CONCLUSION Tuberculosis is a disease which can we #ound in many organs such as the most #ounded in the lungs or we called it pulmonal tuberculosis. The Tuberculosis can we #ound so easily in a patient who have a immunode#iciency syndrome because the patientMs antibodies are in the low level so the body can protect the body itsel#, and the tuberculosis is the most common death in a patient who have a immunode#iciency because o# HIV. * lot o# developing countries become the epidemiology o# Tuberculosis and HIV li-e *#rica, *merica Iatin, ,outh Bast *sia and many more developing countries. There is many actions can we do to prevent the HIV associated Tuberculosis and many treatment to help the patients with this disease but as we -now the preventive action is more important than curative action

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