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      Challenges facing effective implementation of co-trimoxazole prophylaxis in children born to HIV-infected mothers in the public health facilities

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          Abstract

          Background

          If children born to HIV-infected mothers are not identified early, approximately 30% of them will die within the first year of life due to opportunistic infections. In order to prevent morbidity and mortality due to opportunistic infections in children, the World Health Organization recommends the use of prophylaxis using co-trimoxazole. However, the challenges affecting effective implementation of this policy in Tanzania have not been documented.

          Aim

          In this study, we assessed the challenges facing the provision of co-trimoxazole prophylaxis among children born to HIV-infected mothers in the public hospitals of Dar es Salaam, Tanzania.

          Methodology

          Four hundred and ninety-eight infants’ PMTCT (Prevention of Mother-to-Child Transmission of HIV) register books for the past 2 years were reviewed to obtain information regarding the provision of co-trimoxazole prophylaxis. One hundred and twenty-six health care workers were interviewed to identify success stories and challenges in the provision of co-trimoxazole prophylaxis in children. In addition, 321 parents and guardians of children born to HIV-infected mothers were interviewed in the health facilities.

          Results

          Approximately 80% of children were initiated with co-trimoxazole prophylaxis within 2 months after birth. Two hundred and ninety-one (58.4%) children started using co-trimoxazole within 4 weeks after birth. Majority (n=458, 91.8%) of the children were prescribed 120 mg of co-trimoxazole per day, whereas 39 (7.8%) received 240 mg per day. Only a small proportion (n=1, 0.2%) of children received 480 mg/day. Dose determination was based on the child’s age rather than body weight. Parents and guardians reported that 42 (13.1%) children had missed one or more doses of co-trimoxazole during the course of prophylaxis. The majority of health care workers (89.7%) reported that co-trimoxazole is very effective for the prevention of opportunistic infections among children, but frequent shortage of co-trimoxazole in the health facilities was the main challenge.

          Conclusion

          Most children who were initiated with co-trimoxazole prophylaxis did not experience significant opportunistic infections, and the drug was well tolerated. The major barrier for co-trimoxazole prophylaxis was due to frequent out-of-stocks of pediatric co-trimoxazole formulations in the health facilities. Dose determination was based on the age rather than the weight of children, thus creating potential for under- or over-dosing of children.

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          Most cited references28

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          Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda.

          Prophylaxis with co-trimoxazole (trimethoprim-sulphamethoxazole) is recommended for people with HIV infection or AIDS but is rarely used in Africa. We assessed the effect of such prophylaxis on morbidity, mortality, CD4-cell count, and viral load among people with HIV infection living in rural Uganda, an area with high rates of bacterial resistance to co-trimoxazole. Between April, 2001, and March, 2003, we enrolled, and followed up with weekly home visits, 509 individuals with HIV-1 infection and their 1522 HIV-negative household members. After 5 months of follow-up, HIV-positive participants were offered daily co-trimoxazole prophylaxis (800 mg trimethoprim, 160 mg sulphamethoxazole) and followed up for a further 1.5 years. We assessed rates of malaria, diarrhoea, hospital admission, and death. Co-trimoxazole was well tolerated with rare (<2% per person-year) adverse reactions. Even though rates of resistance in diarrhoeal pathogens were high (76%), co-trimoxazole prophylaxis was associated with a 46% reduction in mortality (hazard ratio 0.54 [95% CI 0.35-0.84], p=0.006) and lower rates of malaria (multivariate incidence rate ratio 0.28 [0.19-0.40], p<0.0001), diarrhoea (0.65 [0.53-0.81], p<0.0001), and hospital admission (0.69 [0.48-0.98], p=0.04). The annual rate of decline in CD4-cell count was less during prophylaxis than before (77 vs 203 cells per microL, p<0.0001), and the annual rate of increase in viral load was lower (0.08 vs 0.90 log(10) copies per mL, p=0.01). Daily co-trimoxazole prophylaxis was associated with reduced morbidity and mortality and had beneficial effects on CD4-cell count and viral load. Co-trimoxazole prophylaxis is a readily available, effective intervention for people with HIV infection in Africa.
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            Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial.

            There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality. Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjan's four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital. Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group. In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.
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              Increased disease burden and antibiotic resistance of bacteria causing severe community-acquired lower respiratory tract infections in human immunodeficiency virus type 1-infected children.

              To improve the management of lower respiratory tract infections (LRTI) in human immunodeficiency virus type 1 (HIV-1)-infected children, we assessed the burden of disease, clinical outcome and antibiotic susceptibility of bacteria causing severe community-acquired LRTI in children. A prospective, descriptive study was performed in the pediatric wards at a secondary and tertiary care hospital in South Africa. Urban black children aged 2-60 months admitted with severe acute LRTI from March 1997 through February 1998 were enrolled. HIV-1 infection was present in 45.1% of 1215 cases of severe LRTI. Bacteremia occurred in 14.9% of HIV-1-infected and in 6.5% of HIV-1-uninfected children (P<.00001). The estimated relative incidence of bacteremic severe LRTI in children aged from 2 to 24 months were greater in HIV-1-infected than in -uninfected children for Streptococcus pneumoniae (risk ratio [RR], 42.9; 95% confidence interval [CI], 20.7-90.2), Haemophilus influenzae type b (RR, 21.4; 95% CI, 9.4-48.4), Staphylococcus aureus (RR, 97.9; 95% CI, 11.4-838.2) and Escherichia coli (RR, 49.0; 95% CI, 15.4-156). Isolation of Mycobacterium tuberculosis was also more common in HIV-1-infected than in -uninfected children (RR, 22.5; 95% CI, 13.4-37.6). In HIV-1-infected children, 60% of S. aureus and 85.7% of E. coli isolates were resistant to methicillin and trimethoprim-sulfamethoxazole, respectively. The case-fatality rates among HIV-1-infected children was 13.1%, and among HIV-1-uninfected children, 2.1% (adjusted odds ratio [AOR]; 6.52, 95% CI, 3.53-12.05; P<.00001). The changing spectrum of bacteria and antibiotic susceptibility patterns in HIV-1-infected children requires a reevaluation of the empirical treatment of community-acquired severe LRTI in children from developing countries with a high prevalence of childhood HIV-1 infection.
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                Author and article information

                Journal
                Drug Healthc Patient Saf
                Drug Healthc Patient Saf
                Drug, Healthcare and Patient Safety
                Drug, Healthcare and Patient Safety
                Dove Medical Press
                1179-1365
                2015
                29 October 2015
                : 7
                : 147-156
                Affiliations
                [1 ]Unit of Pharmacology and Therapeutics, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
                [2 ]Department of Medicinal Chemistry, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
                Author notes
                Correspondence: Appolinary AR Kamuhabwa, Unit of Pharmacology and Therapeutics, School of Pharmacy, Muhimbili University of Health and Allied Sciences, PO Box 65013, Dar es Salaam, Tanzania, Tel +255 75 757 6985, Fax +255 22 215 0465, Email akamuhabwa@ 123456muhas.ac.tz
                Article
                dhps-7-147
                10.2147/DHPS.S89115
                4631415
                26604825
                b42f2b56-227a-4a6b-a2b7-13d43fca9e37
                © 2015 Kamuhabwa and Manyanga. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Public health
                health facilities,opportunistic infections,cd4,parents,guardians
                Public health
                health facilities, opportunistic infections, cd4, parents, guardians

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